Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Skrzypczak H, Reed R, Brainard B, Sakai D, Barletta M, Quandt J, Smyth C, Ruch M, Knych H.Matrix fentanyl patches have not been investigated in horses and may represent an effective means of providing analgesia over an extended time period without venous catheterisation. Objective: To describe the pharmacokinetics of a matrix transdermal fentanyl patch in horses. Methods: Randomised experiment, Latin-square design. Methods: Six adult horses were given each of three treatments with a 96-hour washout. For each treatment, two 100 µg/h matrix fentanyl patches were applied to the inguinal region (TXA), metacarpus (TXM) or ventral tail base (TXT) for 72 hours. Blood samples for fentan...
Knych HK, Magdesian KG.Equine antimicrobial therapy has advanced over time with the availability of increasing pharmacokinetic and pharmacodynamic studies in horses, allowing for greater evidence-based clinical decision-making. However, many challenges to optimal antimicrobial therapy remain and further research is needed to address these areas. There are a limited number of approved antimicrobials for use in horses, which creates a need for compounded preparations for clinicians. Extra-label drug use is commonplace in equine practice, which warrants continual education of veterinarians about policies and updates. P...
Trachsel DS, Calloe K, J Rgensen E, Lunddahl CS, Pedersen PJ, Kanters JRK, Klaerke DA, Buhl R.To determine whether administration of trimethoprim-sulfadiazine (TMS), detomidine (DET), or TMS plus DET would be associated with changes in ECG repolarization parameters in horses. Methods: 9 healthy adult horses. Methods: Each horse received 4 treatments in a blinded, randomized, crossover study design as follows: TMS, 16 to 24 mg/kg, IV; DET, 0.015 to 0.02 mg/kg, IV; TMS plus DET; and saline (0.9% NaCl) solution. Surface ECG traces were obtained over 24 hours, and repolarization parameters were measured at predefined time points after each treatment and compared with a 2-way ANOVA for repe...
Shane SE, Langston VC, Wills RW, Denney WS, Knych H, Fontenot RL, Meyer RE, Natalini CC.An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and...
Fenner MF, Gatta G, Sattler S, Kuiper M, Hesselkilde EM, Adler DMT, Smerup M, Schotten U, Sørensen U, Diness JG, Jespersen T, Verheule S....Small-conductance Ca2+-activated K+ (KCa2) channels have been proposed as a possible atrial-selective target to pharmacologically terminate atrial fibrillation (AF) and to maintain sinus rhythm. However, it has been hypothesized that the importance of the KCa2 current-and thereby the efficacy of small-conductance Ca2+-activated K+ current (I K,Ca) inhibition-might be negatively related to AF duration and the extent of AF-induced remodeling. Unassigned: To address the hypothesis of the efficacy of I K,Ca inhibition being dependent on AF duration, the anti-arrhythmic properties of the I K,Ca inh...
McNeal CD, Ryan CA, Berghaus LJ, Credille BC, Lo CP, Fajt VR.Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidim...
Kilcoyne I, Nieto JE, Galuppo LD, Dechant JE.To determine the median time to maximum concentration (t) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses. Methods: 7 healthy adult horses. Methods: With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrur...
Kuroda T, Minamijima Y, Niwa H, Tamura N, Mita H, Fukuda K, Kaimachi M, Suzuki Y, Enoki Y, Taguchi K, Matsumoto K, Toutain PL, Bousquet-Melou A....First-generation cephalosporins have good activity against gram-positive bacteria and are extensively used in horses. There are few reports of pharmacokinetics and pharmacodynamics (PK/PD) analysis of cephalosporins in horses. Objective: To optimise the dosages of the two first-generation cephalosporins cephalothin (CET) and cefazolin (CEZ) in horses using PK/PD concepts. Methods: Experimental study with single administration. Methods: Drug plasma concentrations following a single intravenous (i.v.) administration of 22 mg/kg bodyweight (bwt) CET in 12 horses and of 10 mg/kg bwt CEZ in six h...
Box JR, Karikoski NP, Tanskanen HE, Raekallio MR.Alpha-2-adrenoceptor agonists are sedatives that can cause fluctuations in serum insulin and blood glucose (BG) concentrations in horses. The objectives of this study were to investigate the effects of detomidine and vatinoxan on BG, insulin, and glucagon concentrations in horses with and without insulin dysregulation (ID). In a blinded cross-over design, eight horses with ID and eight horses without ID were assigned to each of four treatments: detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), detomidine + vatinoxan (DET + VAT), and saline control (SAL). Blood samples were taken at 0, ...
Wise JC, Hughes KJ, Edwards S, Jacobson GA, Narkowicz CK, Raidal SL.Omeprazole preparations vary in bioavailability in horses. Objective: To characterize the pharmacokinetics and pharmacodynamics of an existing enteric-coated oral omeprazole paste (REF) and a novel, in-feed, enteric-coated dry granule preparation (NOV). Methods: Twelve Standardbred/Thoroughbred mares free from clinical disease. Methods: A prospective, blinded randomized interventional study was trial, conducted in 3 parts: (a) bioavailability study, (b) dose titration study, and (c) comparative clinical pharmacodynamic study, each using a blocked crossover design. Results: Consistent with the ...
Current drug metabolismDecember 19, 2020
Volume 22, Issue 3 215-223 doi: 10.2174/1389200221666201217141025
Hu SX, Ernst K, Benner CP, Feenstra KL.Pharmacokinetic and pharmacodynamic assessment of ester-containing drugs can be impacted by hydrolysis of the drugs in plasma samples post blood collection. The impact is different in the plasma of different species. Objective: This study evaluated the stability of a prodrug, ketoprofen methylester (KME), in commercially purchased and freshly collected plasma of mouse, rat, dog, cat, pig, sheep, cattle and horse. Methods: KME hydrolysis was determined following its incubation in commercially purchased and freshly collected plasma of those species. Different esterase inhibitors were evaluated f...
Robinson MA, Stefanovski D, You Y, Boston RC, Soma LR.Capsaicinoids deter horses from chewing on bandages and are applied topically to provide analgesia to musculoskeletal injuries. They are banned during competition due to their nerve blocking properties. The pharmacokinetics of oral (PO) and direct gastric administration via nasogastric tube (NG), or topical (TOP) administration of two capsaicinoid-containing products were investigated, and the withdrawal times required prior to competition were estimated. Capsaicin (CAP) and dihydrocapsaicin (DCAP) were quantified in plasma, and both compounds were best described by a delayed absorption two co...
Gittel C, Schulz-Kornas E, Sandbaumhüter FA, Theurillat R, Vervuert I, Larenza Menzies MP, Thormann W, Braun C.To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l-methadone/fenpipramide combination administered to isoflurane anaesthetized ponies. Methods: Prospective single-group interventional study. Methods: A group of six healthy adult research ponies (four mares, two geldings). Methods: Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg) and butorphanol (0.01 mg kg) for an unrelated study. Additional IV detomidine (0.004 mg kg) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg) and keta...
Bousquet-Mélou A, Schneider M, El Garch F, Broussou DC, Ferran AA, Lallemand EA, Triboulloy C, Damborg P, Toutain PL.Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objective: To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Methods: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. M...
Khusro A, Aarti C, Buendía-Rodriguez G, Arasu MV, Al-Dhabi NA, Barbabosa-Pliego A.Antibiotics-based therapy plays a paramount role in equine medicine because of their potential pharmacokinetics and pharmacodynamics properties. Conventional antibiotics show bacteriostatic and bactericidal properties by interfering bacterial cell wall and protein synthesis as well as inhibiting RNA polymerase, DNase 1, and DNA gyrase. Antibiotics are extensively used not only for the treatment of varied bacterial infections but also the prevention of postoperative and secondary infections. Surprisingly, antibiotics such as sulfonamides or trimethoprim/sulfonamide combinations, benzylpenicilli...
Hanafi AL, Reed RA, Trenholme HN, Sakai DM, Ryan CA, Barletta M, Quandt JE, Knych HK.To describe the pharmacokinetics and pharmacodynamics of meperidine after IM and subcutaneous administration in horses. Methods: prospective, randomized, blinded, crossover trial. Methods: Six adult horses weighing 494 ± 33 kg. Methods: Treatments included meperidine 1 mg/kg IM with saline 6 mL subcutaneously, meperidine 1 mg/kg subcutaneously with saline 6 mL IM, and saline 6 mL subcutaneously and 6 mL IM, with a 7-day washout between treatments. Plasma meperidine concentrations and pharmacodynamic values (thermal and mechanical thresholds, physiological variables, fecal production) were c...
Rosa B.Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledg...
Alonso JM, Martins ES, Peccinini RG, Rosa GS, Guerra ST, Ribeiro MG, Santos B, García HDM, Watanabe MJ, Takahira RK, Rodrigues CA, Alves ALG....Intraperitoneal ceftriaxone administration in healthy horses results in high and prolonged peritoneal concentrations. Recent findings suggest that intraperitoneal ceftriaxone might increase survival rates in horses affected by peritonitis. The present study aimed to evaluate plasma and peritoneal concentrations of ceftriaxone after intraperitoneal administration in horses with septic peritonitis. Twenty-six horses presenting clinical, laboratorial, and sonographic findings compatible with the disease were included. All horses received daily intraperitoneal ceftriaxone (25 mg/kg bwt) in additi...
Lee DH, Birhanu BT, Lee EB, Lee SJ, Boby N, Park YS, Park SC.Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefqui...
Hamamoto-Hardman BD, Steffey EP, McKemie DS, Kass PH, Knych HK.Meperidine is a synthetic opioid that belongs to the phenylpiperidine class and is a weak mu receptor agonist. In horses there are a limited number of published studies describing the analgesic effects of systemically administered meperidine in horses. The objective of this study was to describe the pharmacokinetics, behavioral and physiologic effects and effect on thermal threshold of three doses of intravenously administered meperidine to horses. Eight University owned horses (four mares and four geldings, aged 3-8 years were studied using a randomized balanced 4-way cross-over design. Hors...
Alonso BB, La Rosa L, Carregaro AB, Gasthuys F, Schauvliege S.To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80-120 μg kg IV], anesthetic maintenance (40 μg kg hour IV), and recovery (20 μg kg IV) or detomidine (group D), at doses of 10-20 μg kg IV, 5 μg kg hour IV, and 2.5 μg kg IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and fina...
Gustafsson K, Tatz AJ, Dahan R, Britzi M, Soback S, Sutton GA, Kelmer G. The aim of this study was to determine the time (T) to the maximum concentration (C) of amikacin sulphate in synovial fluid of the radiocarpal joint (RCJ) following cephalic intravenous regional limb perfusion (IVRLP) using 2 g of amikacin sulphate. Methods: Cephalic IVRLP was performed with 2 g of amikacin sulphate diluted in 0.9% NaCl to a total volume of 100 mL in six healthy adult mixed breed mares. An Esmarch's rubber tourniquet was applied for 30 minutes and the antibiotic solution was infused through a 23-gauge butterfly catheter. Synovial fluid was collected from the RCJ ...
Knych HK, Finno CJ, Baden R, Arthur RM, McKemie DS.The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of r...
Fenner MF, Carstensen H, Dalgas Nissen S, Melis Hesselkilde E, Scott Lunddahl C, Adler Hess Jensen M, Loft-Andersen AV, Sattler SM, Platonov P....Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. The pharmacological ion channel profile of XAF-1407 was investigated us...
Knych HK, Weiner D, Arthur RM, Baden R, McKemie DS, Kass PH.Corticosteroids are potent anti-inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations. Blood and urine samples were collected prior to and for up to...
Schumacher SA, Toribio RE, Scansen B, Lakritz J, Bertone AL.The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO ) to healthy horses. MgSO is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitor...
Karasek I, Butler C, Baynes R, Werners A.Ectoparasites infestations are a growing concern to horse owners and equine veterinarians alike. Ectoparasites cause significant health and welfare issues and can potentially can serve as vectors for a variety of pathogens. The prevalence of ectoparasites increases around the world, and especially in horses information on the successful prevention and treatment of ectoparasite infestations in scarce and in many instances anecdotal. This poses a challenge to the equine veterinarian and off-label use of drugs can lead to detrimental effects in horses. In this review we describe the current avail...
Ivermectin (IVM) is an anthelmintic compound commonly used off-label in mules due to its broad-spectrum of activity. Despite the general use of IVM in mules with the same dose and route of administration licensed for horses, significant pharmacokinetic differences might exist between horses and mules, as already observed for donkeys. The aim of the present study was to evaluate the pharmacokinetic profile and anthelmintic efficacy of an oral paste of IVM in mules naturally infected with cyathostomins. Fifteen adult mules with fecal egg counts (FEC) ≥200 eggs per gram (EPG), with exclusive pr...
Hopster K, Soma LR, Li X, Hopster-Iversen C, Boston RC, Driessen B.Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg hr for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration-time curves following bolus an...
Tamura N, Okano A, Kuroda T, Niwa H, Kusano K, Matsuda Y, Fukuda K, Mita H, Nagata S.To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis. Methods: Five healthy Thoroughbred horses. Methods: Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0 mg/kg. TF and blood samples were collected before and periodically throughout the 24 hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography-electrospray tandem-mass spectrometry. T...
Grady JA, Davis EG, Kukanich B, Sherck AB.To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses. Methods: 6 adult horses. Methods: Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week in...
Roelvink ME, Goossens L, Kalsbeek HC, Wensing T.The analgesic and spasmolytic effects of dipyrone (Novalgin) (2500 mg/100 kg bodyweight) hyoscine-N-butylbromide (Buscopan) (20 mg/100 kg bodyweight) and a combination of both drugs were evaluated in a balloon-induced model of colic, using five ponies with caecal fistulae. The drugs were given intravenously and 0.9 per cent sodium chloride solution (5 ml/100 kg bodyweight) was used as a control. The physiological saline solution and dipyrone had no effect on caecal contractions. After the injection of hyoscine-N-butylbromide and the drug combination caecal contractions ceased within 30 seconds...
Peters J, Block W, Oswald S, Freyer J, Grube M, Kroemer HK, Lämmer M, Lütjohann D, Venner M, Siegmund W.The delivery of clarithromycin (CRL) to its site of action in bronchial/alveolar epithelial cells (EC), bronchial epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) may be influenced by CYP3A4 and the drug transporters, ATP-binding cassette (ABC) B1 and ABCC2 and organic anion-transporting polypeptides (OATPs), which can be modulated and/or up-regulated via the nuclear pregnane X receptor (PXR) by rifampicin (RIF). Therefore, we evaluated the disposition and pulmonary distribution of CLR (7.5 mg/kg b.i.d., 21 days) and expression of ABCB1, ABCC2, OATP1A2, and OATP2B1 in EC ...
Coakley M, Peck KE, Taylor TS, Matthews NS, Mealey KL.To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
Raidal SL, Andrews FM, Nielsen SG, Trope G.Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. Objective: To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Methods: Masked 2 period, 2 treatment crossover. Methods: Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day...
Meyers KM, Lindner C, Katz J, Grant B.Nonsteroidal anti-inflammatory drugs impair platelet aggregation and secretion in man, pigs, and rabbits and inhibit platelet thromboxane/prostaglandin synthesis. The present investigation studied the effects of phenylbutazone on platelet aggregation and bleeding times in the horse. Aggregation responses to adenosine diphosphate and collagen were markedly impaired 15 minutes and 2 hours after treatment, but 4 hours after treatment, platelet responses approximated those prior to treatment. The in vivo effect of phenylbutazone correlated with its plasma concentrations. Phenylbutazone, like aspir...
Khusro A, Aarti C, Buendía-Rodriguez G, Arasu MV, Al-Dhabi NA, Barbabosa-Pliego A.Antibiotics-based therapy plays a paramount role in equine medicine because of their potential pharmacokinetics and pharmacodynamics properties. Conventional antibiotics show bacteriostatic and bactericidal properties by interfering bacterial cell wall and protein synthesis as well as inhibiting RNA polymerase, DNase 1, and DNA gyrase. Antibiotics are extensively used not only for the treatment of varied bacterial infections but also the prevention of postoperative and secondary infections. Surprisingly, antibiotics such as sulfonamides or trimethoprim/sulfonamide combinations, benzylpenicilli...
Ohmura H, Hiraga A, Aida H, Kuwahara M, Tsubone H.To investigate the effects of repeated atropine injection on heart rate (HR) variability in resting Thoroughbred horses, two microg/ kg of atropine as parasympathetic nervous blockade was injected intravenously every 6 min to a total of 8 microg/kg after intravenous administration of 0.2 mg/kg of propranolol as sympathetic nervous blockade. We recorded electrocardiograms and obtained the HR, then evaluated variation in HR from the power spectrum in terms of low frequency (LF, 0.01-0.07 Hz) power and high frequency (HF, 0.07-0.6 Hz) power. Administration of atropine decreased parasympathetic ne...
Parra-Sanchez A, Lugo J, Boothe DM, Gaughan EM, Hanson RR, Duran S, Belknap JK.To evaluate the pharmacokinetic-pharmacodynamic parameters of enrofloxacin and a low dose of amikacin administered via regional IV limb perfusion (RILP) in standing horses. Methods: 14 adult horses. Methods: Standing horses (7 horses/group) received either enrofloxacin (1.5 mg/kg) or amikacin (250 mg) via RILP (involving tourniquet application) in 1 forelimb. Samples of interstitial fluid (collected via implanted capillary ultrafiltration devices) from the bone marrow (BMIF) of the third metacarpal bone and overlying subcutaneous tissues (STIF), blood, and synovial fluid of the radiocarpal joi...
Müller JM, Wissemann J, Meli ML, Dasen G, Lutz H, Heinzerling L, Feige K.Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
Carstensen H, Hesselkilde EZ, Fenner M, Loft-Andersen AV, Flethøj M, Kanters JK, Sattler SM, Tfelt-Hansen J, Pehrson S, Jespersen T, Buhl R.Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy. Objective: To test whether the efficacy of flecainide is dependent on AF duration. Methods: Nine Standardbred mares. Methods: Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, ...
Womble AY, Giguère S, Lee EA, Vickroy TW.To determine pharmacokinetics of clarithromycin and concentrations in body fluids and bronchoalveolar (BAL) cells of foals. Methods: 6 healthy 2-to 3-week-old foals. Methods: In a crossover design, clarithromycin (7.5 mg/kg) was administered to each foal via IV and intragastric (IG) routes. After the initial IG administration, 5 additional doses were administered IG at 12-hour intervals. Concentrations of clarithromycin and its 14-hydroxy metabolite were measured in serum by use of high-performance liquid chromatography. A microbiologic assay was used to measure clarithromycin activity in seru...
Pinto N, Schumacher J, Taintor J, Degraves F, Duran S, Boothe D.No studies have determined the pharmacokinetics of low-dose amikacin in the mature horse. Objective: To determine if a single i.v. dose of amikacin (10 mg/kg bwt) will reach therapeutic concentrations in plasma, synovial, peritoneal and interstitial fluid of mature horses (n=6). Methods: Drug concentrations of amikacin were measured across time in mature horses (n=6); plasma, synovial, peritoneal and interstitial fluid were collected after a single i.v. dose of amikacin (10 mg/kg bwt). Results: The mean±s.d. of selected parameters were: extrapolated plasma concentration of amikacin at time ze...
Lloyd KC, Stover SM, Pascoe JR, Baggot JD, Kurpershoek C, Hietala S.The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater tha...
Mills ML, Rush BR, St Jean G, Gaughan EM, Mosier D, Gibson E, Freeman L.To determine the serum and synovial fluid concentrations of ceftiofur sodium after intraarticular (IA) and intravenous (IV) administration and to evaluate the morphologic changes after intraarticular ceftiofur sodium administration. Methods: Strip plot design for the ceftiofur sodium serum and synovial fluid concentrations and a split plot design for the cytologic and histopathologic evaluation. Methods: Six healthy adult horses without lameness. Methods: Stage 1: Ceftiofur sodium (2.2 mg/kg) was administered IV. Stage 2: 150 mg (3 mL) of ceftiofur sodium (pHavg 6.57) was administered IA into ...
Roger T, Ruckebusch Y.The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induc...
Orsini JA, Soma LR, Rourke JE, Park M.The pharmacokinetics of amikacin sulfate (AK) were studied in the horse after intravenous (i.v.) and intramuscular (i.m.) administration. Serum (Cs), synovial (Csf) and peritoneal (Cpf) fluid concentrations of the drug were measured. Doses of 4.4, 6.6 and 11.0 mg/kg were given. The concentrations at 15 min following i.v. injection were 30.3 +/- 0.3, 61.2 +/- 6.9 and 122.8 +/- 7.4 micrograms/ml, respectively, for the 4.4, 6.6 and 11.0 mg/kg doses. Mean peak Cs values after the intramuscular injections occurred at 1.0 h post-injection and were 13.3 +/- 1.6, 23.0 +/- 0.6 and 29.8 +/- 3.2 microgra...
Shrestha HK, Beg MA, Burnette RR, Ginther OJ.Horses are about five times more sensitive to the luteolytic effect of prostaglandin F2alpha (PGF) than cattle, as indicated by a recommended clinical dose of 5 mg in horses and 25 mg in cattle. Novel evaluations of the PGF plasma disappearance curves were made in mares and in heifers, and the two species were compared. Mares and heifers (n = 5) of similar body weight were injected (Min 0) intravenously with PGF (5 mg per animal). Blood was sampled every 10 sec until Min 3, every 30 sec until Min 5, every 10 min until Min 60, and every 30 min until Min 240. The mean PGF concentration was great...
Kaartinen L, Panu S, Pyörälä S.Pharmacokinetic behaviour of enrofloxacin was studied in 6 horses after intravenous (i.v.) or intramuscular (i.m.) administration of enrofloxacin (5 mg/kg bwt). Concentration of enrofloxacin and ciproflaxin were measured by high performance liquid chromatography in serum. Antimicrobial activity of the samples was determined with an agar-diffusion technique. Reactions at the site of i.m. injection were monitored clinically and by determination of serum creatine kinase (CK) activity. After i.v. administration, elimination half-life of enrofloxacin was 4.4 h and volume of distribution was 2.3 1/k...
Maher MC, Schnabel LV, Cross JA, Papich MG, Divers TJ, Fortier LA.To determine whether low-dose, low-frequency doxycycline administration is capable of achieving chondroprotective concentrations within synovial fluid (SF) while remaining below minimum inhibitory concentration 90 (MIC90 ) of most equine pathogens and would be an option in the management of osteoarthritis. Objective: To determine whether low-dose, low-frequency oral administration of doxycycline can attain in vivo SF concentrations capable of chondroprotective effects through reduction of matrix metalloproteinase (MMP)-13 activity, while remaining below MIC90 of most equine pathogens. Method...
Casini A, Mastrobuoni G, Terenghi M, Gabbiani C, Monzani E, Moneti G, Casella L, Messori L.The interactions with protein targets of the ruthenium(III) complex imidazolium trans-[tetrachloro(dimethyl sulfoxide)(imidazole)ruthenate(III)], NAMI-A, an effective anticancer and antimetastatic agent now in clinical trials, deserve great attention as they are believed to be at the basis of the mechanism of action of this innovative molecule. Here, we report on the reactions of NAMI-A with two well-known model proteins, namely, hen egg white lysozyme and horse heart cytochrome c; these reactions were investigated by a variety of physicochemical methods, including optical spectroscopy, (1)H N...
Cornelisse CJ, Robinson NE, Berney CE, Kobe CA, Boruta DT, Derksen FJ.Although the efficacy of dexamethasone for the treatment of recurrent airway obstruction (RAO) has been documented, the speed of onset of effect and duration of action are unknown, as is the efficacy of orally administered dexamethasone with or without fasting. Objective: To document the time of onset of effect and duration of action of a dexamethasone solution i.v. or orally with and without fasting. Methods: Protocol 1 used 8 RAO-affected horses with airway obstruction in a crossover design experiment that compared the effect of i.v. saline and dexamethasone (0.1 mg/kg bwt) on pulmonary func...
Törneke K, Ingvast Larsson C, Appelgren LE.Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the be...
Scare JA, Lyons ET, Wielgus KM, Nielsen MK.Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repe...
McFarlane D, Banse H, Knych HK, Maxwell LK.The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as p...
Cook VL, Neuder LE, Blikslager AT, Jones SL.The effect of lidocaine on in vitro migration and adhesion of equine neutrophils was evaluated. Neutrophils were isolated from equine whole blood using a Percoll-gradient centrifugation protocol. Purified neutrophils were incubated with lidocaine at concentrations from 0.1 to 1000 microg/ml for 30 min at 37 degrees C, after calcein loading. Neutrophil integrin-mediated adhesion in response to stimulation with 100 nM LTB(4), 100 nM PAF, or 100 ng/ml IL-8, or integrin-mediated migration in response to stimulation with 100 nM LTB(4), 150 nM PAF, or 100 ng/ml IL-8 was assessed. Statistical signifi...
Combie J, Shults T, Nugent EC, Dougherty J, Tobin T.The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more tha...
Gomaa N, Uhlig A, Schusser GF.Seven adult, healthy, conscious warmblood horses were used in a crossover study. They were fed twice a day on 1 kg hay/100 kg BW and 0.5 kg concentrates with unlimited access to water. One hour after feeding, the contractive motility of the descending duodenum, cecal body and left ventral colon were measured using a 5 MHz transcutaneus ultrasonographic transducer. Each horse was treated with 0.9% NaCl (5 ml/100 kg BW; i.v.), and with Buscopan compositum (BC) at its therapeutic dosage (25 mg/kg BW; metamizol-sodium, 0.2 mg/kg BW; N-butylscopolammonium bromide, i.v.) in a control and an experime...
Lees P, McKellar Q, May SA, Ludwig B.The pharmacokinetics and pharmacodynamics of the nonsteroidal anti-inflammatory drug (NSAID) carprofen have been evaluated in 6 horses using a model of acute non-immune inflammation. Following intravenous administration of 0.7 mg racemic carprofen/kg bwt, mean values for pharmacokinetic parameters were 18.1 h (elimination half-life); 0.25 l/kg (volume of distribution, Vd[area]); 58.9 ml/min (clearance); and 57.9 micrograms/ml.h (area under plasma concentration time curve). Mean exudate:plasma concentration ratios exceeded 1.0 at all sampling times between 2 and 48 h. Swelling at the site of ac...
Freeman SL, England GC.The effects of two intravenous doses of romifidine (80 and 120 microg/kg) and one dose of detomidine (20 microg/kg) were compared in a blinded study in 30 horses requiring to be sedated for routine dental treatment. Several physiological parameters were assessed before and for two hours after the administration of the drugs, and the horses' teeth were rasped 30 minutes after they were administered. Romifidine produced a dose-dependent effect on most parameters. Detomidine at 20 microg/kg was similar to romifidine at 120 microg/kg in the magnitude of its sedative effects, but was similar to rom...
