Pharmacokinetics of intravenous and intragastric cimetidine in horses. I. Effects of intravenous cimetidine on pharmacokinetics of intravenous phenylbutazone.

The research article investigates how cimetidine, a medication used to treat ulcers in the stomach and intestines, is processed by the body of horses when given intravenously and through the intragastric route. It also explores the effect of cimetidine on the pharmacokinetics of another medication, phenylbutazone.

Research Methodology

• The researchers administered cimetidine to six mares, giving a dose of 4.0 mg/kg of the horses’ body weight.
• The cimetidine was administered both intravenously and by the intragastric route, allowing for a comparison of the pharmacokinetic profiles via these two methods of administration.
• The levels of cimetidine in the horses’ plasma and urine and cimetidine sulfoxide in urine were determined using specific high performance liquid chromatographic methods.
• The researchers used non-linear least squares regression analysis to examine the plasma cimetidine concentration vs. time data.

Research Findings

• The plasma clearance of cimetidine was found to have a median (range) of 8.20 (4.96-10.2) mL/min.kg of body weight.
• The steady-state volume of distribution was found to have a median (range) of 0.771 (0.521-1.15) L/kg body weight, and the terminal elimination half-life had a median (range) of 92.4 (70.6-125) minutes.
• The renal clearance of cimetidine had a median (range) of 4.08 (2.19-6.23) mL/min.kg body weight, which accounted for 55.4 (36.3-81.8)% of the plasma clearance.
• Cimetidine sulfoxide, a metabolite of cimetidine, was found in the urine, and its excretion accounted for 12.0 (9.8-16.6)% of the plasma clearance of cimetidine over 8 hours.
• The intragastric bioavailability of cimetidine had a median (range) of 14.4 (6.82-21.8)% with a maximum plasma concentration of 0.31 (0.24-0.50) microgram/mL after intragastric administration.

Impact of Cimetidine on Pharmacokinetics of Phenylbutazone

• The study also investigated the effect of cimetidine on the disposition of phenylbutazone, a pain and fever reducing medication often used in horses.
• Results indicated intravenous cimetidine had no significant effect on the disposition of intravenous phenylbutazone or its metabolites. The only observed effect was that the maximum plasma concentration of gamma-hydroxyphenylbutazone was lower after cimetidine treatment.