Analyze Diet

Topic:Metabolites

Metabolites are small molecules involved in the metabolic processes within a horse's body. They are the intermediates and products of metabolism, encompassing a wide range of compounds, such as amino acids, lipids, carbohydrates, and nucleotides. These molecules play roles in energy production, growth, and cellular repair. The study of equine metabolites, often conducted through metabolomics, provides insights into the physiological and pathological states of horses. Changes in metabolite levels can indicate alterations in metabolic pathways, potentially reflecting health conditions or responses to environmental factors. This page compiles peer-reviewed research studies and scholarly articles that explore the identification, function, and diagnostic potential of metabolites in equine health.
Suppress or Not to Suppress … CRAFT It: A Targeted Metabolomics Case Study Extracting Essential Biomarker Signals Directly from the Full 1H NMR Spectra of Horse Serum Samples.
Metabolites    June 10, 2025   Volume 15, Issue 6 387 doi: 10.3390/metabo15060387
Chen J, Yablon A, Metaxas C, Guedin M, Hu J, Conover K, Simpson M, Ralston SL, Krishnamurthy K, Pelczer I.: There are a few very specific inflammation biomarkers in blood, namely lipoprotein NMe signals of protein clusters (GlycA and GlycB) and a composite resonance of phospholipids (SPC). The relative integrals of these resonances provide clear indication of the unique metabolic changes associated with disease, specifically inflammatory conditions, often related to serious diseases such as cancer or COVID-19 infection. Relatively complicated, yet very efficient experimental methods have been introduced recently (DIRE, JEDI) to suppress the rest of the spectrum, thus allowing measurement of these ...
Pharmacokinetics of Chloramphenicol and Chloramphenicol Glucuronide in Horses Following Administration Per Rectum or via Nasogastric Intubation.
Journal of veterinary pharmacology and therapeutics    May 26, 2025   doi: 10.1111/jvp.13520
Sayler B, Manship AJ, Davis J, Taylor J, Gilliam L.Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chl...
Targeted pretreatment and inoculation strategies for horse manure fermentation: Impact on metabolites and microbial community composition.
Journal of environmental management    May 21, 2025   Volume 387 125894 doi: 10.1016/j.jenvman.2025.125894
Pipereau K, Trably E, Santa-Catalina G, García-Bernet D, Carrere H.Horse manure is a lignocellulosic biomass found in significant quantities with a vast indigenous flora, not yet fully valorized apart from anaerobic digestion. Its use in the fermentation process can lead to the production of higher-value metabolites. This study investigates three inoculation strategies coupled with five pretreatment conditions for horse manure fermentation. Two microwave pretreatments (200W and 1000W) were compared with a conventional thermal pretreatment, a thermo-acid pretreatment, and an unpretreated condition. The sole horse manure indigenous microorganisms were used in f...
Doping Control of Ranitidine in Horses.
Drug testing and analysis    May 20, 2025   doi: 10.1002/dta.3909
Ho HSM, Mizzi JX, Ho ENM, Wong WT.Ranitidine is a histamine H-receptor antagonist commonly used to treat gastric ulceration in horses. The author's laboratory conducted a study some years ago in the early 2000s on its metabolism as well as its urinary elimination profile in two geldings. With the technology advancement as well as popularity of blood for doping control testing, the laboratory has recently conducted another administration trials of the substance in six horses to study the in vivo metabolism of ranitidine, aiming to identify and reinvestigate the appropriate target(s) for controlling misuse of ranitidine in hors...
Confirmation of a novel, stable estrogen metabolite, as 5a,6a-epoxy-estrone sulfate in stallion blood by LC-MS/MS.
The Journal of steroid biochemistry and molecular biology    May 20, 2025   Volume 252 106788 doi: 10.1016/j.jsbmb.2025.106788
Raeside JI, Christie HL, Chenier T, Brewer D, Charchoglyan A.Mass spectrometry (MS) has become pivotal for accurately delineating intricate molecular structures for steroids present in minute quantities within biological samples. This study utilized liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) to identify and characterize a 'new' estrogen metabolite, 5α,6α-epoxy-estrone sulfate, in stallion serum from three animals. The estrogen structure was predicted previously using radiolabeled steroids. HRMS/MS, in combination with a seamless sample preparation involving liquid-liquid extraction and chromatographic separation, enabl...
Population pharmacokinetics and clinical evaluation of intravenous acetaminophen and its metabolites in Andalusian horses.
Veterinary journal (London, England : 1997)    April 24, 2025   Volume 312 106357 doi: 10.1016/j.tvjl.2025.106357
Granados MM, Medina-Bautista F, Navarrete-Calvo R, Argüelles D, Domínguez-Pérez JM, Priego-Capote F, Muñoz-Rascón P, Serrano-Rodríguez JM.To date, no intravenous pharmacokinetics (PK) studies have assessed acetaminophen or its major metabolites (acetaminophen-glucuronide and acetaminophen-sulphate) in horses. The influence of sex on acetaminophen metabolism in horses is unclear, and Monte Carlo simulations have not been applied to explore potential clinical applications. This study aimed to determine the intravenous PK and safety of acetaminophen in Andalusian horses at 10 and 20 mg/kg, evaluate sex as a covariate, and simulate clinical regimens. Twenty mares and twenty stallions received intravenous acetaminophen, and plasma ...
Lipidomics and biochemical profiling of adult Yili horses in a 26 km endurance race: exploring metabolic adaptations.
Frontiers in veterinary science    April 22, 2025   Volume 12 1597739 doi: 10.3389/fvets.2025.1597739
Chang X, Zhang Z, Yao X, Meng J, Ren W, Zeng Y.The equine lipid metabolism is activated during and after endurance exercise to provide energy in response to the metabolic and physiological changes in the body caused by prolonged exercise; however, the specific regulatory mechanisms remain controversial and identifying differential lipid metabolites associated with equine endurance is essential to elucidate these regulatory mechanisms. In this study, blood samples for lipid metabolomic analysis and biochemical indices were collected before and after a 26 km race from 12 Yili horses with different endurance performance. The biochemical res...
Endogenous Nature of Hydrocortisone Acetate in Horse.
Drug testing and analysis    April 14, 2025   doi: 10.1002/dta.3897
Kong FKW, Wong ASY, Wan TSM, Ho ENM.Hydrocortisone acetate, a synthetic acetate ester of hydrocortisone, was detected in horse blood samples collected from Thoroughbreds. Hydrocortisone acetate is generally considered an indicator for exogenous administration in horses. As hydrocortisone acetate has been previously reported to be endogenous in selected mammals, a proof-of-concept study was performed to evaluate the possible endogenous nature of hydrocortisone acetate in horses by in vitro incubation experiments using homogenized horse brain tissue.
Physiological and behavioral parameters of pain and stress in mares during and after transvaginal ultrasound-guided follicular aspiration.
Frontiers in veterinary science    April 9, 2025   Volume 12 1574351 doi: 10.3389/fvets.2025.1574351
Van den Branden E, Salamone M, Broothaers K, Peere S, Polfliet E, Dewulf M, Van Steenkiste G, van Loon G, Smits K, Govaere J.The use of transvaginal ultrasound-guided follicle aspiration (TVA) for oocyte collection has become a widely used procedure in horses for embryo production (IVEP). The TVA procedure is characterized by various manipulations, which are physical restraint, perineal preparation, transrectal palpation, insertion of an intravaginal device, and needle punctures. These repeated transvaginal and transovarian punctures have raised concerns about their potential effects on mare welfare. Our study aimed to investigate the effects of TVA manipulations, and especially puncturing, on pain and stress in ma...
In Vivo Metabolic Studies of 2-Hydroxyethyl Salicylate in Horses.
Drug testing and analysis    March 12, 2025   doi: 10.1002/dta.3885
Ho HSM, Farrington AF, Ho ENM, Wong WT.2-Hydroxyethyl salicylate (2HES), a nonsteroidal anti-inflammatory drug (NSAID), is a medication to treat musculoskeletal injuries and inflammation swelling of humans and horses. Its misuse could affect the performance of horses and mask injuries, which could pose significant health risks. In horseracing, it is reported as an adverse finding once detected in competition. The metabolism of 2HES in either human or horse has not been reported, and therefore, little is known about its metabolic fate. This paper describes the in vivo metabolism of 2HES in horse with an objective to identify the mo...
Absolute Quantitative Lipidomics Reveals Differences in Lipid Compounds in the Blood of Trained and Untrained Yili Horses.
Veterinary sciences    March 10, 2025   Volume 12, Issue 3 255 doi: 10.3390/vetsci12030255
Wang T, Meng J, Wang J, Ren W, Yang X, Adina W, Bao Y, Zeng Y, Yao X.The purpose of this study was to explore the relationship between blood lipid levels and the differences in cardiac structure and function of trained and untrained Yili horses as related to exercise performance. We utilized quantitative lipidomics technology to elucidate how the differences in lipid compounds in the blood influenced performance outcomes. Sixteen 18-month-old Yili horses were selected, ten of which received a 15-week training regimen, and six were kept as untrained controls. Cardiac structure and function were assessed by echocardiography, while plasma lipid metabolites were de...
Regulatory Mechanisms of Yili Horses During an 80 km Race Based on Transcriptomics and Metabolomics Analyses.
International journal of molecular sciences    March 8, 2025   Volume 26, Issue 6 doi: 10.3390/ijms26062426
Wang J, Ren W, Li Z, Li L, Wang R, Ma S, Zeng Y, Meng J, Yao X.Equine endurance exercise induces physiological changes that alter metabolism and molecular pathways to maintain balance after intense physical activity. However, the specific regulatory mechanisms remain under debate. Identifying differentially expressed genes (DEGs) and differential metabolites (DMs) associated with equine endurance is essential for elucidating these regulatory mechanisms. This study collected blood samples from six Yili horses before and after an 80 km race and conducted transcriptomics and metabolomics analyses, yielding 722 DEGs and 256 DMs. These DEGs were primarily enri...
Synthesis and Characterization of 3-Hydroxybupivacaine and Deuterated 3-Hydroxybupivacaine for Use in Equine Medication Regulation.
Journal of labelled compounds & radiopharmaceuticals    March 4, 2025   Volume 68, Issue 3 e4132 doi: 10.1002/jlcr.4132
Arojojoye AS, Holmes J, Buchart MP, Awuah SG, Eisenberg R, Fenger CK, Maylin GA, Tobin T.Bupivacaine is a local anesthetic widely used in equine and human medicine. Use of bupivacaine in performance horses is regulated because its ability to block pain means that it can be misused for advantage in performance horses. In racing regulation, bupivacaine is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 Penalty Class A Foreign substance, the detection of which can lead to significant penalties. In horses, bupivacaine is metabolized by Phase-I hydroxylation to yield 3-hydroxybupivacaine, which is then glucuronidated to yield the Phase-II metabol...
The Impact of the Competition on miRNA, Proteins, and Metabolites in the Blood Exosomes of the Yili Horse.
Genes    February 15, 2025   Volume 16, Issue 2 224 doi: 10.3390/genes16020224
Yuan X, Yao X, Zeng Y, Wang J, Ren W, Wang T, Li X, Yang L, Yang X, Meng J.Horse racing may cause stress-induced physiological changes and tissue damage in horses, but the changes in miRNA expression, protein expression, and metabolic substances in the plasma exosomes of the horse after racing are still unclear. This study detected miRNA, protein expression, and metabolic substances in the plasma exosomes of horses before and after competition, providing new insights for post-race recovery and care of horses. Methods: Eight three-year-old horses that had undergone training were selected as the research subjects, with four horses that had not competed as the contr...
Convolutional Neural Networks Assisted Peak Classification in Targeted LC-HRMS/MS for Equine Doping Control Screening Analyses.
Analytical chemistry    February 3, 2025   Volume 97, Issue 6 3236-3241 doi: 10.1021/acs.analchem.4c03608
Barnabé A, Delcourt V, Loup B, Montanuy W, Trévisiol S, Popot MA, Garcia P, Bailly-Chouriberry L.Doping control screening analyses usually involve visual inspection of extracted ion chromatograms (EIC) by a trained analytical chemist, followed by further investigations if needed. This task is both highly repetitive and time-consuming, given the hundreds of compounds and metabolites to be screened in tens of thousands of samples per year. With the recent widespread adoption of machine learning in analytical chemistry and the training of high-performance convolutional neural networks (CNN), these operations can be automated with high accuracy and throughput. Applying this technology to dopi...
Equine endometrial bacteria inhibition by metabolite and extracellular vesicles of Lactobacillus acidophilus and lactiplantibacillus plantarum.
Veterinary research communications    January 2, 2025   Volume 49, Issue 1 61 doi: 10.1007/s11259-024-10626-3
Bernabe MCM, Fonseca BB, Silva MVC, Pedrosa IE, Silva MB, Sommerfeld S, de Sousa ALP, de Leva Resende BC, Sousa ACP, Dos Santos Freitas A....Endometritis is one of the main reproductive disorders in mares and due to the increasing prevalence of antibiotic resistance, the use of probiotics in the prevention and treatment of endometritis in mares has gained interest, given their potential to restore and maintain a healthy uterine microbiota. Therefore, the aim of this study was to evaluate the antimicrobial properties of total metabolites of Lactobacillus acidophilus (LA) and Lactiplantibacillus plantarum (LP) against common equine endometrial pathogenic bacteria in vitro (Acinetobacter baumannii, Escherichia coli (1), Escherichia co...
Further Investigation Into an Environmental Source for Aminorex.
Drug testing and analysis    December 18, 2024   Volume 17, Issue 8 1357-1367 doi: 10.1002/dta.3820
Brooks L, Ryan M, McCosham E, Loganathan D.In 2009, levamisole was identified as a source for several aminorex positives reported in postrace equine samples in Canada. Since then, unexplained detections of aminorex continue to be identified in equine samples where there is no evidence to link these detections to a levamisole administration. Previous studies identified a compound named barbarin in some species of plants from the Brassicaceae family and suggested that barbarin may be a possible precursor for aminorex. The objectives of this study were to (1) investigate the link between barbarin and aminorex and (2) identify other biomar...
Detection of Over 110 Anabolic-Androgenic Steroids, Corticosteroids and/or Their Esters in Horse Hair Using Ultra-High-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and Gas Chromatography-Tandem Mass Spectrometry After Solid-Supported Liquid Extraction.
Drug testing and analysis    December 10, 2024   doi: 10.1002/dta.3837
So YM, Kwok WH, Ching CCW, Wong COL, Wan TSM, Ho ENM.Anabolic-androgenic steroids (AAS) are banned substances in both human and equine sports. They are often administered intramuscularly to horses in esterified forms for the purpose of extending their duration of action. As such, the detection of intact esters of endogenous steroids in hair is particularly advantageous, as it can provide unequivocal proof of their external origin. Compared with urine and blood matrices, hair in general allows a longer detection window as long as the administered drug can be incorporated into hair and has not degraded. This can be useful in doping control of equi...
Essential oil supplementation improves insulin sensitivity and modulates the plasma metabolome of hyperinsulinemic horses.
Frontiers in veterinary science    December 2, 2024   Volume 11 1444581 doi: 10.3389/fvets.2024.1444581
Loos CMM, Zhao S, Li L, Li J, Han W, Vanzant ES, McLeod KR.The objective of this study was to investigate the effect of essential oil (EO) supplementation on insulin sensitivity (IS) and the plasma metabolome in insulin dysregulated (ID) horses. Horses were blocked by degree of IS and assigned randomly to treatment: oral daily bolus (50 mL) of either a plant derived EO supplement or carrier (CON). Mares were housed in dry lots with access to grass hay and supplemented individually twice daily with a concentrate to meet nutrient requirements for mature horses. Before and after 6 wks of treatment, mares underwent a combined glucose-insulin tolerance ...
Investigation Into the Equine Metabolism of Phosphodiesterase-4 Inhibitor Roflumilast for Potential Doping Control.
Drug testing and analysis    November 17, 2024   doi: 10.1002/dta.3822
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Graiban FM, Ajeebsanu MM, Joseph M, Jose SV.The phosphodiesterase 4 (PDE4) inhibitors constitute a relatively modern class of medications that are known for inducing bronchodilation and exhibiting anti-inflammatory properties within the body. Due to these properties, there is concern regarding their potential misuse as performance-enhancing substances in competitive sports. This study delves into the metabolic conversion of roflumilast in thoroughbred horses following oral administration and in vitro experimentation using equine liver microsomes and Cunninghamella elegans. High-performance liquid chromatography coupled with a Q Exactiv...
Identification of altered blood metabolic pathways in equines following ethyl pyruvate administration using non-targeted metabolomics.
Scientific reports    November 12, 2024   Volume 14, Issue 1 27684 doi: 10.1038/s41598-024-75734-1
Kwak YB, Seo SA, Kim M, Yoon J.Ethyl pyruvate (EP) has emerged as a promising compound with potential therapeutic benefits attributed to its anti-inflammatory and antioxidant properties. This study aimed to understand the effects of EP on plasma metabolites and immune cells in horses, utilizing advanced liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, quantitative polymerase chain reaction (qPCR), and blood chemistry analyses. Our comprehensive analysis detected 2,366 ions, and 126 metabolites were accurately identified. Remarkably, EP administration induced significant changes in 28 metabolites at 1 h a...
Unraveling the genetic and physiological potential of donkeys: insights from genomics, proteomics, and metabolomics approaches.
Mammalian genome : official journal of the International Mammalian Genome Society    November 7, 2024   doi: 10.1007/s00335-024-10083-y
Parsad R, Bagiyal M, Ahlawat S, Arora R, Gera R, Chhabra P, Sharma U.Donkeys (Equus asinus) have played a vital role in agriculture, transportation, and companionship, particularly in developing regions where they are indispensable working animals. The domestication of donkeys marked a significant turning point in human history, as they became essential for transportation, agriculture, and trade, especially in arid and semi-arid areas where their resilience and endurance were highly valued. In modern society, donkeys are indispensable due to their diversified applications, including meat, dairy, medicine, and functional bioproducts, supporting economic, cultura...
Influence of Loading Density and Gender on the Welfare and Meat Quality of Horses During Transport for Slaughter.
Animals : an open access journal from MDPI    October 24, 2024   Volume 14, Issue 21 3069 doi: 10.3390/ani14213069
Božić Jovanović V, Trailović R, Vićić I, Grković N, Radaković M, Karabasil N, Kaić A, Čobanović N.The aim of this study was to determine the effects of loading density and gender on blood welfare indicators, carcass bruises and horsemeat quality. Data were collected from twelve transports of 89 slaughter horses originating from the same collection centre. The transportation of slaughter horses at high loading densities (>200 kg/m), especially stallions, resulted in increased levels of lactate ( = 0.021), glucose ( < 0.0001), ceruloplasmin ( < 0.0001) and AOPP ( < 0.0001), but lower GSH levels ( 200 kg/m) during transport had lower levels of the aforementioned blood metabolites....
Administration Route Differentiation of Altrenogest via the Metabolomic LC-HRMS Analysis of Equine Urine.
Molecules (Basel, Switzerland)    October 22, 2024   Volume 29, Issue 21 4988 doi: 10.3390/molecules29214988
Elbourne M, Keledjian J, Cawley A, Fu S.Altrenogest, also known as allyltrenbolone, is a synthetic form of progesterone used therapeutically to suppress unwanted symptoms of estrus in female horses. Altrenogest affects the system by decreasing levels of endogenous gonadotrophin and luteinizing and follicle-stimulating hormones, which in turn decreases estrogen and mimics the increase of progesterone production. This results in more manageable mares for training and competition alongside male horses while improving the workplace safety of riders and handlers. However, when altrenogest is administered, prohibited steroid impurities su...
Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine).
Domestic animal endocrinology    October 5, 2024   Volume 90 106891 doi: 10.1016/j.domaniend.2024.106891
Galinelli NC, Bamford NJ, Erdody ML, Warnken T, de Laat MA, Sillence MN, Harris PA, Bailey SR.Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic anal...
Metabolomic analysis of the impact of red ginseng on equine physiology.
Frontiers in veterinary science    September 30, 2024   Volume 11 1425089 doi: 10.3389/fvets.2024.1425089
Kwak YB, Stambler I, Yoo HH, Yoon J.Red ginseng (RG), a traditional herbal remedy, has garnered attention owing to its diverse health benefits resulting from its complex composition. However, extensive research is needed to substantiate the efficacy of RG and understand the underlying mechanisms supporting these benefits. This study aimed to identify potential biomarkers and investigate the impact of RG on related metabolic pathways in horse plasma using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Unassigned: Ten horses were divided into control and RG groups, with the latter administered RG at a dose of ...
Equine metabolic investigation of the phosphodiesterase-4 inhibitor ibudilast as a potential performance enhancer.
Rapid communications in mass spectrometry : RCM    September 23, 2024   Volume 38, Issue 23 e9916 doi: 10.1002/rcm.9916
Philip M, Kal AKK, Subhahar MB, Karatt TK, Graiban FM, Ajeebsanu MM, Joseph M, Jose SV.Phosphodiesterase 4 (PDE4) inhibitors are a newer class of drugs that induce bronchodilation and have anti-inflammatory effects, making them susceptible to misuse as performance enhancers in competitive sports. Methods: This study explores the metabolic conversion of PDE4 inhibitor ibudilast in thoroughbred horses after oral administration and in vitro using equine liver microsomes and Cunninghamella elegans. A liquid chromatography-high resolution mass spectrometry method was used to postulate the plausible structures of the detected metabolites. Results: A total of 20 in vivo metabolites wer...
Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’.
Molecular human reproduction    September 17, 2024   Volume 30, Issue 9 doi: 10.1093/molehr/gaae033
No abstract available
Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’.
Molecular human reproduction    September 17, 2024   Volume 30, Issue 9 gaae033 doi: 10.1093/molehr/gaae033
Walter J, Colleoni S, Lazzari G, Fortes C, Grossmann J, Roschitzki B, Laczko E, Naegeli H, Bleul U, Galli C.Assisted reproductive technologies are an emerging field in equine reproduction, with species-dependent peculiarities, such as the low success rate of conventional IVF. Here, the 'cumulome' was related to the developmental capacity of its corresponding oocyte. Cumulus-oocyte complexes collected from slaughterhouse ovaries were individually matured, fertilized by ICSI, and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS)-based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total o...
Detection of levamisole and its metabolites in horses after oral levamisole administration over seven days.
Journal of the American Veterinary Medical Association    September 13, 2024   Volume 262, Issue 12 1632-1638 doi: 10.2460/javma.23.06.0340
Adam E, Scollay M, Howard B, Taormina J, Hartmann P, Knych H.Levamisole is a regulated substance sometimes administered to racehorses to treat equine protozoal myelitis. Metabolites include compound II, aminorex, and pemoline. Aminorex and pemoline are Horseracing Integrity and Safety Authority-banned substances. Previous studies have examined single doses of the drug. This study examined the disposition of levamisole after 7 days of dosing. Methods: 6 healthy Thoroughbred geldings. Methods: Horses were treated with 500 mg (approx 0.91 to 1 mg/kg) of compounded levamisole hydrochloride paste PO every 12 hours for a total of 13 doses over 7 days. Serum a...