Pharmacokinetics horses

Benoit, E. Jaussaud, P. Besse, S. Videmann, B. Courtot, D. Delatour, P. Bonnaire, Y. Identification of a benzhydrolic metabolite of ketoprofen in horses by gas chromatography-mass spectrometry and high-performance liquid chromatography. J.Chromatogr., 1992, 583, 167—173 [plasma SPE gradient extracted metabolites LOQ 500 ng/mL LOD 100 ng/mL pharmacokinetics horse]... 

Phenothiazines (acepromazine, propio-promazine, promazine, trimepra-zine, methotrimeprazine, thioridazine, chlorpromazine) 7.5-64,000 2.2-66.5 1.0-3.7 Acepromazine was determined in horse plasma with good results the method is suitable for pharmacokinetic studies 43... 

Pharmacokinetic studies with horse chestnut focus on the absorption, metabolism, and excretion of the main constituent—p-aescin. 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

Little is known about the pharmacokinetics and biotransformation of acepromazine in food-producing animals. After intramuscular injection of 0.1 mg/ kg bw to horses, the unchanged acepromazine was detectable in plasma 1.5-3 h... 

Pharmacokinetic studies in horses, cattle, sheep, and dogs have shown that the differences between the four species were remarkably small (112). After intravenous administration of xylazine, systemic half-lives ranged from 22 min... 

To determine the safety of using lithium chloride dilution to measure cardiac output, the pharmacokinetic and toxic effects of intravenous lithium chloride have been studied in six conscious healthy Standardbred horses (527). The mean peak serum concentration was 0.56 mmol/1. There were neither toxic effects nor significant changes in laboratory studies, electrocardiograms, or gastrointestinal motility. Three horses had increased urine output. 

Hatfield CL, McDonell WN, Lemke KA, Black WD. Pharmacokinetics and toxic effects of hthium chloride after intravenous administration in conscious horses. Am J Vet Res 2001 62(9) 1387-92. 

The 2-arylpropionic acid ( profen ) non-steroidal anti-inflammatory drugs, each of which contains a single chiral center, are formulated as racemic (50 50) mixtures of the S(+)- and R(-)-enantiomers, with the exception of naproxen, which is formulated as the S(- -)-enantiomer. Based on inhibition of cyclooxygenase activity, the S(- -)-enantiomer is the eutomer (more potent enantiomer). These drugs differ markedly in both pharmacodynamic activity and pharmacokinetic behavior and, in addition, enantiomer pharmacokinetics of each drug varies among animal species. After intravenous administration of racemic keto-profen to horses, sheep, and 20-week-old calves and measurement of individual enantiomers in plasma, significant differences between the enantiomers were found in systemic clearance in horses and in both systemic clearance and volume of distribution in sheep... 

Table 14 Pharmacokinetic parameters describing disposition of S(+)- and R(—)-enantiomers after intravenous administration of racemic ketoprofen (KTP) to horses (n = 6) and sheep (n = 6)...

Landoni, M.F. Lees, P. Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses. J. Vet. Pharmacol. Ther. 1995c, 18, 446-450. 

Lizarraga, I. Sumano, H. Brumbaugh, G.W. Pharmacological and pharmacokinetic differences between donkeys and horses. Equine Vet. Educ. 2004, 62, 130-144. 

Figure 11.1 Ion current of the phenylbutazone daughter ions for a 60-sample, 48-h pharmacokinetic study in the horse using high-speed LC-MS-MS. Reprinted from [1] with permission, 1986, American Chemical Society.

Pharmacokinetics of gentamicin in the horse. American Journal of Veterinary Research 41 351-354 Riviere J E 1999 Comparative pharmacokinetics principles, techniques and applications. Iowa State University Press, Ames, lA, pp. 47-61 Sp>echt T E, Brown M P, Qronwall R R et al 1992 Pharmacokinetics of metronidazole and its... 

Although there is limited pharmacokinetic information available in horses, these agents appear to be similar to other penicillins. Following i.v. injection of ticarcillin to horses, at a dose rate of 44 mg/kg, the serum concentration at 30 min was 104.3 jjig/1 and the mean peak peritoneal fluid concentration (61.4(i,g/l) was reached 2h after injection. The half-life of ticarcillin was 0.94 h. Following i.m. injection (44 mg/kg), the peak serum (28.3 xg/l) and peritoneal fluid (19.2 xg/l) concentrations were reached after 2h. The bioavailability of ticarcillin was 64.9%. 

Pharmacokinetic studies have not been performed in horses however, i.v. doses of 0.7-1.Img/kg three times a day have been suggested as being suitable for use in small animals. Imipenem has to be administered i.v. because it is not absorbed following p.o. administration. Imipenem has been shown to penetrate inflamed meninges. It is metabolized extensively by the renal tubules to a potentially toxic compound. Therefore, it is usually combined with cilastatin, a drug that inhibits the renal tubular enzymes. The combined product produces high urine concentrations of active antibiotic and avoids renal toxicity. In the presence of cilastatin, 70% of a dose of imipenem is excreted unchanged in the urine. The half-life of imipenem in the dog is 30-45 nrin. 

In horses, 75-100% of a gentamicin dose is excreted unchanged in the urine in the first 8-24 h after administration. The half-life is 1-2 h and is longer in neonatal foals than in older foals and adult horses. Any gentamicin that accumulates in the renal cortical tissue is eliminated slowly however, these levels are often below the limits of quantification of the assays used and are, therefore, not demonstrated in pharmacokinetic studies. 

Florfenicol is associated with producing transient diarrhea in calves and has been associated anecdotally with severe colitis in horses. In one pharmacokinetic study, all of the horses and ponies developed mild diarrhea following i.v., i.m. or p.o. administration of florfenicol. In a recent study where the commercial florfenicol formulation was administered i.m. to horses at 20mg/kg every 48 h, all of the horses remained clinically normal but showed significant changes in commensal fecal flora. High numbers of Clostridium perfringens and Salmonella spp. were isolated from some of the treated horses. Florfenicol should be used with caution in horses because of its potential to induce antimicrobial-associated colitis. 

Based upon pharmacokinetic information and minimal inhibitory concentrations (MIC) for pyrimethamine, an oral daily dose of Img/kg in combination with 22 mg/kg sulfadiazine is recommended in horses. The duration of treatment is controversial and the recommendations range from a minimum of 3 months (least conservative) to the point at which the CSF is seronegative (most conservative). It is clear that the latter course of treatment is least likely to result in relapse of the clinical signs (Fenger 1997), but it is likely that this exceeds what is absolutely necessary in most cases. 

Dirikolu L, Lehner F, Nattrass C et al 1999 Diclazuril In the horse its identification and detection and preliminary pharmacokinetics. Journal of Veterinary Pharmacology and Therapeutics 22 374-379 Fenger C K 1997 Equine protozoal myeloencephalitis. Compendium on Continuing Education for the Practicing Veterinarian 19 513... 

Paterson S, Orrell S 1995 Treatment of biting lice (Damalinia equi) in 25 horses using 1 % selenium sulphide. Equine Veterinary Education 7 304-306 Pereira M C, Kohek I Jr, Campos R et al 1991 A field evaluation of antheimintics for control of cyathostomes of horses in Brazil. Veterinary Parasitoiogy 38 121-129 Perez R, Cabezas i, Garcia M et al 1999 Comparison of the pharmacokinetics of moxidectin (Equest ) and ivermectin (Eqvalan ) in horses. Journai of Veterinary Pharmacology and Therapeutics 22 174-180... 

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