Pharmacokinetics and metabolism of FCE 22101 following its administration as the oral pro-drug FCE 22891

Abstract

Ten healthy male volunteers who had previously received both intramuscular and intravenous doses of FCE 22101 received a single oral dose of FCE 22891, the acetoxymethyl ester and pro-drug of FCE 22101. After a lag time of 22 min, mean plasma levels of FCE 22101 rose with a T1/2 absorbance of 19 min to 2.5 mg/L at 30 min, 3.6 mg/L at 60 min and a Cmax of 4.6 mg/L at 80 min; levels then fell with a T1/2 beta of 29 min to be undetectable at 300 min. The mean area under the concentration-time curve (AUC) was 497 mg.min/L giving an absolute bioavailability for FCE 22101 of 32%. Neither FCE 22101 or its metabolites were present in any of the saliva samples collected at intervals up to 360 min after dosing. Mean urinary recoveries were FCE 22101 12% (+/- S.D. 4.6), P1 16% (+/- S.D. 9.1) and P2 3.3% (+/- S.D. 2.1). It was not possible to detect the pro-drug FCE 22891 in any of the blood or urine samples. Significant levels of the metabolite P1 were observed in blood with peak levels of 1.7 mg/L seen 130 min after dosing, 50 min later than the peak FCE 22101 levels, and giving a mean AUC of 297 mg.min/L.