PHARMACOKINETICS OF INTRAVENOUS AND INTRAGASTRIC CIMETIDINE IN HORSES.1. EFFECTS OF INTRAVENOUS CIMETIDINE ON PHARMACOKINETICS OF INTRAVENOUS PHENYLBUTAZONE

Cimetidine was administered intravenously and by the intragastric rout e to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific an d sensitive high performance liquid chromatographic methods for the de termination of cimetidine in horse plasma and urine and cimetidine sul foxide in urine are described. Plasma cimetidine concentration vs. tim e data were analysed by non-linear least squares regression analysis t o determine pharmacokinetic parameter estimates. The median (range) pl asma clearance (Cl) was 8.20 (4.96-10.2) mL/min.kg of body weight, tha t of the steady-state volume of distribution (Vd(ss)) was 0.771 (0.521 -1.15) L/kg bw, and that of the terminal elimination half-life (t(1/2 beta)) was 92.4 (70.6-125) minutes. The median (range) renal clearance of cimetidine was 4.08 (2.19-6.23) mL/min.kg bw or 55.4 (36.3-81.8)% of the corresponding plasma clearance. Cimetidine sulfoxide was excret ed in urine and its urinary excretion through 8 h accounted for 12.0 ( 9.8-16.6)% of the plasma clearance of cimetidine. The median (range) e xtent of intragastric bioavailability was 14.4 (6.82-21.8)% and the ma ximum plasma concentration after intragastric administration was 0.31 (0.24-0.50) mu g/mL. Intravenous cimetidine had no effect on the dispo sition of intravenous phenylbutazone or its metabolites except that th e maximum plasma concentration of gamma-hydroxyphenylbutazone was less after cimetidine treatment.