Pharmacokinetics and pharmacodynamics of antiulcer agents in llama

Plasma concentration time curves following intravenous (i.v.) administratio n of 1.5 mg/kg of ranitidine, 0.2 mg/kg, 0.4 mg/kg and 0.8 mg/kg of omepraz ole, respectively, were analysed in six llamas. Plasma profiles after i.v. administration of both drugs showed plasma concentrations declining in a bi exponential manner with a rapid distribution phase. Pharmacokinetics parame ters after ranitidine administration to six llamas showed a mean eliminatio n half-life of 1.53 +/- 0.26 h. The mean volume of distribution (V-dss) in llamas was 1.77 +/- 0.31 L/kg, and mean body clearance in llamas was 0.778 +/- 0.109 L/ kg/h. Ranitidine produced only a small transitory (<1 h) decli ne in acid production when administered i.v. at a dose of 1.5 mg/kg. Omepra zole showed dose-dependent nonlinear pharmacokinetics. The mean half-life o f 0.2 mg/kg i.v. omeprazole was shorter than that of 0.4 and 0.8 mg/kg i.v. omeprazole, i.e. 0.61, 0.72 and 1.07 h, respectively. The area under the c urve (AUC) and mean residence time (MRT) increased with increasing dose, wh ile clearance decreased as dose increased. The decline in acid production f ollowing 0.2 mg/kg i.v. omeprazole was highly variable and did not produce a clinically useful suppression of third compartment acid production. In co ntrast, both 0.4 mg/kg and 0.8 mg/kg omeprazole i.v. administration signifi cantly reduced third compartment acid production. The reduction in acid pro duction following 0.8 mg/kg omeprazole was not significantly greater than t he reduction observed following 0.4 mg/kg dosage. Misoprostol (10 <mu>g/kg) was administered i.v. in an absolute alcohol solution, Two animals collaps ed following drug administration. While the side-effects could have been pr oduced by either misoprostol or the alcohol vehicle, the clinical changes w ere more consistent with an adverse drug reaction. Unfortunately, the limit ation of UV detection did not provide the sensitivity needed to quantify th e amount of misoprostol in llama plasma, and the pharmacokinetics could not be evaluated.