Pharmacokinetics of intravenous and intragastric cimetidine in horses. I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone.
Cimetidine was administered intravenously and by the intragastric route to six mares at a dose of 4.0 mg/kg of body weight (bw). Specific and sensitive high performance liquid chromatographic methods for the determination of cimetidine in horse plasma and urine and cimetidine sulfoxide in urine are described. Plasma cimetidine concentration vs. time data were analysed by non-linear least squares regression analysis to determine pharmacokinetic parameter estimates. The median (range) plasma clearance (Cl) was 8.20 (4.96-10.2) mL/min.kg of body weight, that of the steady-state volume of distribution (Vdss) was 0.771 (0.521-1.15) L/kg bw, and that of the terminal elimination half-life (t1/2 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 excreted 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) extent of intragastric bioavailability was 14.4 (6.82-21.8)% and the maximum plasma concentration after intragastric administration was 0.31 (0.24-0.50) microgram/mL. Intravenous cimetidine had no effect on the disposition of intravenous phenylbutazone or its metabolites except that the maximum plasma concentration of gamma-hydroxyphenylbutazone was less after cimetidine treatment.
Sams
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Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, Columbus 43210, USA.
Gerken
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Dyke
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Reed
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Ashcraft
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SM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002927:Cimetidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000652:urine; D006736:Horses; D007267:Injections; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D010113:Oxyphenbutazone / Q000097:blood; D010653:Phenylbutazone / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012044:Regression Analysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D010653:Phenylbutazone; C034042:cimetidine sulfoxide; D010113:Oxyphenbutazone