Meperidine pharmacokinetics following intravenous, peroral and buccal administration in beagle dogs

The pharmacokinetics of meperidine was studied in Beagle dogs following intravenous, peroral and buccal administration of a meperidine hydrochloride solution. The elimination half-life after I.V., P.O. and buccal routes was 0.75 +/- 0.14 hours, 0.93 +/- 0.18 hours and 0.36 +/- 0.10 hours, respectively. The volume of distribution and total clearance following I.V., P.O. and buccal administration were 2.41 +/- 0.34 L/kg and 42.5 +/- 8.9 ml/min/kg, 2.84 +/- 1.24 L/kg and 34.6 +/- 7.8 ml/min/kg, 1.01 +/- 0.52 L/kg and 34.7 +/- 8.0 ml/min/kg, respectively. The absolute bioavailability after P.O. and buccal administration was 11.0 +/- 6.8% and 11.9 +/- 6.6%, respectively. This paper discusses the observed low bioavailabilities on hypothesis of hepatic and lung first-pass effect. A hypothesis is presented to explain the delayed onset of absorption following buccal administration.