Topic:Dosage

Why the racing industry and equestrian disciplines need to implement population pharmacokinetics: To learn, explain, summarize, harmonize, and individualize.
Drug testing and analysis    April 29, 2024   doi: 10.1002/dta.3706
Toutain PL.Population pharmacokinetics (POP PK) is a powerful pharmacokinetic tool, which measures quantitatively, and explains the variability in drug exposure and drug effect between individuals. POP PK uses an observational (nonexperimental) approach; it is conducted in the target population living in its normal environment (e.g., farm and race-track). The strength of the POP PK approach lies in its greater relevance for the population studied in its different natural environments than experimental studies carried out in more or less biased laboratory conditions. In clinical settings, it is commonly n...
Trimethoprim-sulfonamide: a valid antimicrobial treatment in foals?
Journal of the American Veterinary Medical Association    March 13, 2024   1-9 doi: 10.2460/javma.23.09.0536
Gustafsson K, Sykes BW, Verwilghen D, Palmers K, Sullivan S, van Galen G.Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are re...
Pharmacokinetic/pharmacodynamic analysis of cephalothin after intramuscular administration in Thoroughbred horses.
Journal of equine science    January 18, 2024   Volume 34, Issue 4 111-114 doi: 10.1294/jes.34.111
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Ohta M.A pharmacokinetic/pharmacodynamic (PK/PD) approach was used to determine a dosage regimen of cephalothin (CET) after intramuscular (IM) administration in horses. CET plasma concentrations were measured in eight horses after a single IM administration of 11 mg/kg bwt of CET. The data were modeled using a nonlinear mixed-effect model, and the probability of target attainment (PTA) of the PK/PD target was calculated for 5,000 horses generated by Monte Carlo simulations. IM administrations of CET at 11 mg/kg bwt q 8 hr and q 6 hr achieved a PTA of 90% against the MIC of S. zooepidemicus and S. aur...
Condition optimization for electroporation transfection in horse skeletal muscle satellite cells.
Animal biotechnology    November 20, 2023   1-9 doi: 10.1080/10495398.2023.2280664
Ulaangerel T, Yi M, Budsuren U, Shen Y, Ren H, Demuul B, Bai D, Dorjgotov D, Davaakhuu G, Jambal T, Dugarjav M, Bou G.Satellite cells are an important cellular model for studying muscle growth and development and mammalian locomotion-related molecular mechanisms. In this study, we investigated the effects of voltage, pulse duration, and DNA dosage on horse skeletal muscle satellite cells' electroporation transfection efficiency using the eukaryotic expression plasmid Td Tomato-C1 (5.5 kb) encoding the red fluorescent protein gene mainly based on fluorescence-positive cell rate and cell survival rate. By comparison of different voltages, pulse durations, and DNA doses, horse skeletal muscle satellite cells h...
Therapeutic Medications and Illicit Medications and Supplements.
The Veterinary clinics of North America. Equine practice    November 9, 2023   S0749-0739(23)00069-X doi: 10.1016/j.cveq.2023.10.003
Hovda LR.This article provides information on the toxicity of some therapeutic drugs, illicit drugs, and supplements. Medications in the therapeutic section are grouped into antibiotics, antipsychotic agents, bronchodilators, nonsteroidal anti-inflammatory drugs, opioids, and sedatives/tranquilizers. The section on illicit drugs and supplements provides information on more specific medications including commonly used or abused human medications and a few that are available only from Internet compounding pharmacies. Many drugs and supplements can be either therapeutic or illicit depending on the dosage ...
Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.
Frontiers in microbiology    October 25, 2023   Volume 14 1282949 doi: 10.3389/fmicb.2023.1282949
Lallemand EA, Bousquet-Mu00e9lou A, Chapuis L, Davis J, Ferran AA, Kukanich B, Kuroda T, Lacroix MZ, Minamijima Y, Olsu00e9n L, Pelligand L....The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses. Unassigned: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 ...
Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses.
Cells    October 24, 2023   Volume 12, Issue 21 2513 doi: 10.3390/cells12212513
Burk J, Wittenberg-Voges L, Schubert S, Horstmeier C, Brehm W, Geburek F.The treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone through block randomization (dosage adapted to lesion size). Clinicians and horse owners...
The effects of feeding sodium chloride pellets on the gastric mucosa, acid-base, and mineral status in exercising horses.
Journal of veterinary internal medicine    September 30, 2023   Volume 37, Issue 6 2552-2561 doi: 10.1111/jvim.16851
Alshut F, Venner M, Martinsson G, Vervuert I.Electrolyte supplementation may be a risk factor for gastric mucosal lesions, but relevant evidence is limited in horses. Objective: Investigate the effects of PO sodium chloride (NaCl) supplementation on the gastric mucosa of exercising horses. We hypothesized that NaCl supplementation would neither cause nor exacerbate existing gastric mucosal damage. Methods: Fifteen 3-year-old healthy Warmblood stallions from a stud farm. Methods: Placebo-controlled study with a crossover design. Horses were fed either a NaCl pellet at a dosage adequate to replace the electrolyte losses in 10 L sweat or ...
Pharmacokinetic-Pharmacodynamic Study of Ampicillin-Cloxacillin Combination in Indian Thoroughbred Horses (Equus caballus) and Safety Evaluation of the Computed Dosage Regimen.
Journal of equine veterinary science    May 21, 2022   Volume 115 104020 doi: 10.1016/j.jevs.2022.104020
Kondampati KD, Saini SPS, Sidhu PK, Anand A, Kumar D, Beesam S, Bedi JS, Kaur R, Bhardwaj R.The pharmacokinetics of ampicillin-cloxacillin, given as single intravenously dose of 10 mg.kg (5 mg.kg of ampicillin plus 5 mg.kg of cloxacillin) was examined in clinically presented Indian thoroughbred horses (n = 6) in order to design appropriate dosing strategies. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived by non-compartmental analysis using WinNonlin software. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ampicillin-cloxacillin against quality cont...
Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses.
Journal of veterinary pharmacology and therapeutics    December 17, 2021   Volume 45, Issue 2 188-195 doi: 10.1111/jvp.13041
Redmond JS, Stang BV, Schlipf JW, Christensen JM.Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non-fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1 mg/kg intravenously, 1 mg/kg intragastrically, and 5 mg/kg...
Pharmacokinetic Evaluation of a Cannabidiol Supplement in Horses.
Journal of equine veterinary science    December 17, 2021   Volume 110 103842 doi: 10.1016/j.jevs.2021.103842
Williams MR, Holbrook TC, Maxwell L, Croft CH, Ientile MM, Cliburn K.Cannabidiol (CBD) products have gained popularity among horse owners despite limited evidence regarding pharmacokinetics. The purpose of this study was to describe the pharmacokinetic profile of multiple doses of an orally administered cannabidiol product formulated specifically for horses. A randomized 2-way crossover design was used. Seven horses received 0.35 or 2.0 mg/kg CBD per os every 24 hours for 7 total doses, separated by a 2-week washout. Plasma CBD and delta-9-tetrahydrocannabinol (THC) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) daily through da...
Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses.
Genes    November 24, 2021   Volume 12, Issue 12 1874 doi: 10.3390/genes12121874
Dahlgren AR, Knych HK, Arthur RM, Durbin-Johnson BP, Finno CJ.Recombinant human erythropoietin (rHuEPO) is a well-known performance enhancing drug in human athletes, and there is anecdotal evidence of it being used in horse racing for the same purpose. rHuEPO, like endogenous EPO, increases arterial oxygen content and thus aerobic power. Micro-doping, or injecting smaller doses over a longer period of time, has become an important concern in both human and equine athletics since it is more difficult to detect. Horses offer an additional challenge of a contractile spleen, thus large changes in the red blood cell mass occur naturally. To address the challe...
Pharmacokinetics of low-dose methotrexate in horses.
Journal of veterinary pharmacology and therapeutics    March 26, 2020   Volume 43, Issue 5 461-469 doi: 10.1111/jvp.12857
Rostang A, Desjardins I, Espana B, Panzuti P, Berny P, Prouillac C, Pin D.This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concen...
Clinical utility, dose determination, and safety of ocular contrast-enhanced ultrasonography in horses: A pilot study.
Veterinary ophthalmology    December 4, 2019   Volume 23, Issue 2 331-340 doi: 10.1111/vop.12730
Blohm KO, Tichy A, Nell B.To determine efficacy of contrast-enhanced ultrasonography (CEUS) using different sulfur hexafluoride (SF6) doses to assess blood flow and perfusion in equine eyes and to evaluate safety of SF6 in horses. Methods: Ocular B-mode and contrast-enhanced ultrasonography were performed bilaterally in nine sedated university-owned horses. Intravenous SonoVue® bolus injections of 5, 10, 15, 20, 25, and 30 mL were administered for 2/18, 5/18, 6/18, 3/18, 1/18, and 1/18 eyes, respectively. Doses were increased based on ascending bodyweight. Each eye within one horse was examined utilizing a different ...
Retrospective evaluation of clinical use of cis-atracurium in horses.
PloS one    August 15, 2019   Volume 14, Issue 8 e0221196 doi: 10.1371/journal.pone.0221196
Tutunaru A, Dupont J, Gougnard A, Ida K, Serteyn D, Sandersen C.To the authors' knowledge, there are no reports describing the use of cis-atracurium in the horse. To describe the onset time and the duration of the neuromuscular blockade (NMB) of three different doses of cis-atracurium in horses and to determine the appropriate dose needed maintain a NMB. Retrospective study. Horses which received cis-atracurium as part of a balanced anaesthetic protocol at the Equine Teaching Hospital of the University of Liège between March 2014 and June 2017 were included in this study. A train-of-four (TOF) stimulation pattern was used to assess the NMB. The cis-atracu...
Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses.
Journal of veterinary pharmacology and therapeutics    June 20, 2019   Volume 42, Issue 5 525-529 doi: 10.1111/jvp.12770
Langston VC, Fontenot RL, Byers JA, Andrews CM, Mochal-King CA.The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples ...
Pharmacokinetics, metabolism and excretion of celecoxib, a selective cyclooxygenase-2 inhibitor, in horses.
Journal of veterinary pharmacology and therapeutics    March 19, 2019   Volume 42, Issue 5 518-524 doi: 10.1111/jvp.12757
Subhahar MB, Singh J, Albert PH, Kadry AM.Celecoxib, a nonsteroidal anti-inflammatory drug, is frequently used to treat arthritis in humans with minimal gastrointestinal side effect compared to traditional NSAIDs. The primary aim of this study was to determine the pharmacokinetic profile of celecoxib-a selective cyclooxygenase-2 (COX-2) inhibitor in horses. Six horses were administered a single oral dose of celecoxib at 2 mg/kg (body weight). After oral dosing, the drug reached a maximum concentration (mean ± SD) in blood of 1,088 ± 324 ng/ml in 4.58 hr. The elimination half-life was 13.60 ± 3.18 hr, and the area under th...
Specific bioactive collagen peptides (PETAGILE® ) as supplement for horses with osteoarthritis: A two-centred study.
Journal of animal physiology and animal nutrition    April 7, 2018   Volume 102 Suppl 1 16-23 doi: 10.1111/jpn.12863
Dobenecker B, Reese S, Jahn W, Schunck M, Hugenberg J, Louton H, Oesser S.The aim of the study was to evaluate the clinical efficacy of specific bioactive collagen peptides (BCP), here administered orally as PETAGILE , on horses with mild to moderate, naturally occurring osteoarthritis. Data from a two-centred pilot study were used for the meta-analysis. Thirty-eight privately owned horses of various breeds were available. In one centre, 18 of these patients (6 ± 3 years; 519 ± 100 kg BW) received either 25 g (n = 6) or 50 g (n = 12) BCP/day orally for 12 weeks. In the second centre, 20 horses (18 ± 4 years; 413 ± 94 kg BW) received either a p...
In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses.
Journal of veterinary pharmacology and therapeutics    June 10, 2017   Volume 41, Issue 1 98-104 doi: 10.1111/jvp.12425
Bianco AW, Moore GE, Cooper BR, Taylor SD.Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inh...
Suspected aspirin resistance in individual healthy adult warmblood horses.
Journal of veterinary pharmacology and therapeutics    April 7, 2017   Volume 40, Issue 6 e16-e22 doi: 10.1111/jvp.12408
Roscher KA, Failing K, Schenk I, Moritz A.The reasons for this prospective experimental study were to determine a dosing scheme with loading and maintenance dose of aspirin inducing inhibition of platelet function measured by whole blood impedance aggregometry. Ten horses received aspirin orally in the morning with one loading dose of 4.7-5 mg/kg and maintenance doses of 1-1.3 mg/kg daily the following 4 days. Aggregometries (COLtest, ASPItest, ADPtest) and serum salicylic acid were measured. ASPItest showed significant difference in inhibition at 24 and 48 hr (p < .05) and 96 hr (p < .01). Significant change for ADPtes...
Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses.
Journal of veterinary pharmacology and therapeutics    September 18, 2016   Volume 40, Issue 3 239-247 doi: 10.1111/jvp.12362
Uney K, Altan F, Altan S, Erol H, Arican M, Elmas M.The plasma and synovial fluid pharmacokinetics and safety of cefquinome, a 2-amino-5-thiazolyl cephalosporin, were determined after multiple intravenous administrations in sixteen healthy horses. Cefquinome was administered to each horse through a slow i.v. injection over 20 min at 1, 2, 4, and 6 mg/kg (n = 4 horses per dose) every 12 h for 7 days (a total of 13 injections). Serial blood and synovial fluid samples were collected during the 12 h after the administration of the first and last doses and were analyzed by a high-performance liquid chromatography assay. The data were evaluate...
Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability.
Equine veterinary journal    June 24, 2016   Volume 49, Issue 3 352-357 doi: 10.1111/evj.12590
Edmonds RE, Garvican ER, Smith RK, Dudhia J.To provide evidence to support recommendations regarding the co-administration of drugs with mesenchymal stem cell (MSC) therapy. Objective: To determine the influence of sedatives, local anaesthetic and corticosteroids on MSC viability and proliferation, in comparison to somatic cells derived from tendon (TDCs). Methods: In vitro cell culture. Methods: MSCs (n = 3) and TDCs (n = 2) were cultured in media containing a clinically relevant dose range of xylazine, romifidine, detomidine and butorphanol, mepivacaine, methylprednisolone, or triamcinolone acetonide. Cell viability in suspension cult...
Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.
Journal of veterinary pharmacology and therapeutics    October 1, 2014   Volume 38, Issue 3 227-234 doi: 10.1111/jvp.12164
Swain EA, Magdesian KG, Kass PH, Edman JE, Knych HK.Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics wi...
Comparison of the effect of two doses of omeprazole on the squamous gastric mucosa in thoroughbred racehorses.
The Veterinary record    August 5, 2014   Volume 175, Issue 10 249 doi: 10.1136/vr.102622
Sykes BW, Sykes K, Hallowell GD.No abstract available
A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial.
Equine veterinary journal    November 24, 2013   Volume 46, Issue 4 416-421 doi: 10.1111/evj.12191
Sykes BW, Sykes KM, Hallowell GD.Studies on omeprazole have reported that doses as low as 0.7 mg/kg bwt per os are potent suppressors of acid production. Yet, to date, no studies have compared treatment efficacy of different doses in clinical cases of equine gastric ulceration. Furthermore, no studies have been performed to compare the healing response of the squamous and glandular mucosa to acid suppression therapy. Objective: To compare: 1) the efficacy of 2 doses of omeprazole in the treatment of primary squamous and glandular gastric ulceration; and 2) the healing response of primary squamous and glandular gastric ulcer...
Phase I dose escalation of doxorubicin chemotherapy in tumor-bearing equidae.
Journal of veterinary internal medicine    July 26, 2013   Volume 27, Issue 5 1209-1217 doi: 10.1111/jvim.12145
Thu00e9on AP, Pusterla N, Magdesian KG, Wilson WD.There is no information on the use of doxorubicin in horses with tumors. Objective: To determine dose-limiting toxicosis (DLT) and maximum tolerated dose (MTD) of doxorubicin in tumor-bearing horses. Methods: Seventeen horses with 34 localized or multicentric advanced tumors. Methods: Two-stage dose-ranging design involving intrapatient and interpatient dose escalation. Treatment protocol included 6 treatment cycles given at 3-week intervals with dosages ranging from 40 to 85 mg/m(2). Clinical signs, hematologic, and nonhematologic changes were evaluated. Results: Total doses ranged from 1,127...
Comparing the pharmacokinetics of a fourth generation cephalosporin in three different age groups of New Forest ponies.
Equine veterinary journal. Supplement    May 19, 2012   Issue 41 52-56 doi: 10.1111/j.2042-3306.2011.00501.x
Smiet E, Haritova A, Heil BA, Fink-Gremmels J, Wijnberg ID.To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. Methods: Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. Results: Both foal age groups had comparable pharmacokinetic data e...
Assessment of the sedative effects of buprenorphine administered with 20 microg/kg detomidine in horses.
The Veterinary record    April 11, 2011   Volume 168, Issue 15 409 doi: 10.1136/vr.c7315
Love EJ, Taylor PM, Murrell J, Whay HR, Waterman-Pearson AE.The aim of this randomised, observer-blinded, crossover study was to compare the effects of four treatments, administered intravenously to six horses: saline and saline; 10 µg/kg detomidine and 7.5 µg/kg buprenorphine; 20 µg/kg detomidine and 7.5 µg/kg buprenorphine; and 20 µg/kg detomidine and 10 µg/kg buprenorphine. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation and duration of sedation were investigated using a univariate general linear model with post-hoc Tukey tests (P<0.05). Increasing the dose of detomidine from 10 to 20 µg/kg increas...
Pharmacokinetics and pharmacodynamics of three intravenous doses of yohimbine in the horse.
Journal of veterinary pharmacology and therapeutics    September 10, 2010   Volume 34, Issue 4 359-366 doi: 10.1111/j.1365-2885.2010.01234.x
Dimaio Knych HK, Steffey EP, Stanley SD.Yohimbine is an alpha 2 adrenergic receptor antagonist, which has been shown to counteract the CNS depressant effects of alpha 2 receptor agonists in a number of species. Recently, our laboratory identified yohimbine in the absence of detectable concentrations of an alpha 2 agonist in a regulatory sample collected from a horse racing in California. This coupled with anecdotal reports of CNS stimulation and documented reports of cardiovascular changes when administered in conjunction with an agonist led us to investigate the pharmacokinetics and pharmacodynamics of yohimbine when administered a...
Pharmacokinetics and tissue distribution of minocycline hydrochloride in horses.
American journal of veterinary research    September 3, 2010   Volume 71, Issue 9 1062-1066 doi: 10.2460/ajvr.71.9.1062
Nagata S, Yamashita S, Kurosawa M, Kuwajima M, Hobo S, Katayama Y, Anzai T.To determine the pharmacokinetics and tissue distribution of minocycline in horses. Methods: 5 healthy Thoroughbred mares for the pharmacokinetic experiment and 6 healthy Thoroughbred mares for the tissue distribution experiment. Methods: Each mare was given 2.2 mg of minocycline hydrochloride/kg, IV. Blood samples were collected once before minocycline administration (0 hours) and 10 times within 48 hours after administration in the pharmacokinetics study, and 24 tissue samples were obtained at 0.5 and 3 hours in the distribution study. Results: No adverse effects were observed in any of the ...
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