Plasma pharmacokinetics of ranitidine HCl in adult horses

Abstract

Plasma pharmacokinetics of ranitidine HCl were investigated after intravenous (i.v.) and oral (p.o.) administration of 2.2 mg/kg drug to six healthy adult horses. Concentrations of ranitidine were determined using normal-phase, high-performance liquid chromatography. Plasma concentrations of ranitidine HCl declined from a mean of 5175 ng/mL at 5 min to 37 ng/mL at 720 min after i.v. administration. A three-exponent equation, Cp = A1 x e-k1t + A2 x e-k2t + A3 x e-k3t, best described data for all horses. Mean values for model-independent values calculated from the last quantifiable time point were: apparent volume of distribution (Vdss) = 1.07 L/kg; area under the curve (AUC) = 231,000 ng.min/mL: area under the moment curve (AUMC) = 26,900,000 ng.min2/mL; mean residence time (MRT) = 113 min; and clearance (Cl) = 9.8 mL/min.kg. Following p.o. administration, a two-exponent equation, Cp = A1 x e-k1t + A2 x e-k2t, best described the data for five horses: data for the remaining horse were best described by a three-exponent equation. Mean values of pharmacokinetic values from the p.o. study include: AUC = 59,900 ng x min/mL; AUMC = 10,600,000 ng x min2/mL; mean absorption time (MAT) = 58.9 min: Tmax = 99.2 min; Cmax = 237 ng/mL: and F = 27%.

Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses

“…Ranitidine was administered over 5 minutes because rapid administration in clinical cases had resulted in colic signs (cramping) in the authors' experience. Ranitidine concentrations were not measured in the present study, but results of a different study indicated that the maximal concentration of ranitidine reached in vivo via IV infusion of a 2.2 mg/kg dose was approximately 5,175 ng/mL, which corresponds to 1.475 10 −5 M. 30 This concentration was maintained only for a short time after IV injection and was substantially lower than the concentration that was effective in vivo (10 −4 M). Furthermore, administration of acetaminophen to the horses in the present study was performed 15 minutes after treatment with ranitidine or placebo, a time at which the plasma concentration of ranitidine would have been even lower.…”

Efficacy of a pectin‐lecithin complex for treatment and prevention of gastric ulcers in horses

“…Unfortunately, at the time of the study, no formulations of omeprazole were available for the use in horses in the country. The use of H 2 blockers was evaluated; however, efficacy of H 2 blockers to induce complete healing of ulceration has been shown to be variable (Murray and Eichorn 1996, Holland and others 1997, Orsini and others 2003). …”

Disposition of the anti‐ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses

“…The terminal serum half‐life of cimetidine and ranitidine in the current study was prolonged (7.05 ± 1.02 h and 7.43 ± 0.851) compared to previous reports describing administration to horses (cimetidine: 2.23 ± 0.64 h (3.3 and 10 mg/kg PO), Smyth et al ., ; 92.4 min (4.0 mg/kg intragastric), Sams et al ., ; ranitidine: 84.7 min (2.2 mg/kg PO), Holland et al ., ). This difference is likely attributable to the more sensitive analytical assay utilized in the current study (LOQ of 0.05 ng/mL) as compared to the previous studies (250 ng/mL, Sams et al ., ; 30 ng/mL, Holland et al ., ) or in the case of cimetidine, differences in sampling protocols. Blood samples were collected for a prolonged period of time, in the current study (48‐h postadministration of the final dose) relative to the study by Sams et al .…”

“…They are all classified, by the Association of Racing Commissioners International (ARCI), as class 5 foreign substances, and as such their use is regulated in horse racing. While the pharmacokinetics of cimetidine, ranitidine, and omeprazole following a single administration have been reported (Sams et al ., ; Smyth et al ., ; Holland et al ., ; Duran & Ravis, ), to the authors' knowledge, there are no reports describing serum concentrations or the disposition of these drugs following multiple administrations, which is commonplace in performance horse practice.…”