TY - JOUR
T1 - The disposition and pharmacokinetics of ketoconazole in the rat
AU - Remmel, R. P.
AU - Amoh, K.
AU - Abdel-Monem, M. M.
PY - 1987
Y1 - 1987
N2 - The disposition, biliary excretion, and pharmacokinetics of ketoconazole in Sprague-Dawley rats were determined after intravenous administration. Greater than 80% of the radioactivity after a 5 mg/kg iv dose of 3H-ketoconazole was excreted in the feces. Urinary excretion was essentially complete after 48 hr; however, fecal excretion was prolonged over a 7-day period. Biliary excretion of radioactivity averaged 54.3 ± 18.0% of the dose over a 7.5-8-hr period in pentobarbital-anesthesized rats. The possibility of enterohepatic recirculation was examined using a linked rat technique. Less than 2% of the radioactivity was found in the recipient bile over 9-12 hr. In eight male rats, the plasma pharmacokinetics of ketoconazole, as determined by an HPLC assay with fluorescence detection, were as follows: V(D) = 655 ± 91 ml/kg, Cl = 14.4 ± 5.1 ml/min/kg, and t 1/2 = 35.0 ± 12.3 min. Three of the rats were given an additional oral dose to determine absolute bioavailability. The time to peak was 30-60 min, and the bioavailability was 35.8 ± 3.55%. Previous studies have indicated that ketoconazole is well absorbed in rats; therefore, the poor bioavailability is probably due to first pass metabolism. The prolonged fecal excretion of radioactivity from an intravenous dose was probably caused by slow elimination of ketoconazole metabolites.
AB - The disposition, biliary excretion, and pharmacokinetics of ketoconazole in Sprague-Dawley rats were determined after intravenous administration. Greater than 80% of the radioactivity after a 5 mg/kg iv dose of 3H-ketoconazole was excreted in the feces. Urinary excretion was essentially complete after 48 hr; however, fecal excretion was prolonged over a 7-day period. Biliary excretion of radioactivity averaged 54.3 ± 18.0% of the dose over a 7.5-8-hr period in pentobarbital-anesthesized rats. The possibility of enterohepatic recirculation was examined using a linked rat technique. Less than 2% of the radioactivity was found in the recipient bile over 9-12 hr. In eight male rats, the plasma pharmacokinetics of ketoconazole, as determined by an HPLC assay with fluorescence detection, were as follows: V(D) = 655 ± 91 ml/kg, Cl = 14.4 ± 5.1 ml/min/kg, and t 1/2 = 35.0 ± 12.3 min. Three of the rats were given an additional oral dose to determine absolute bioavailability. The time to peak was 30-60 min, and the bioavailability was 35.8 ± 3.55%. Previous studies have indicated that ketoconazole is well absorbed in rats; therefore, the poor bioavailability is probably due to first pass metabolism. The prolonged fecal excretion of radioactivity from an intravenous dose was probably caused by slow elimination of ketoconazole metabolites.
UR - http://www.scopus.com/inward/record.url?scp=0023609211&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023609211&partnerID=8YFLogxK
M3 - Article
C2 - 2893696
AN - SCOPUS:0023609211
SN - 0090-9556
VL - 15
SP - 735
EP - 739
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 6
ER -