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Nonlinear pharmacokinetics of aprindine in guinea pigs.

Abstract：

:After intravenous bolus administration of aprindine (AP) to conscious guinea pigs, the semilogarithmic plasma concentration versus time curve was linear at a dose of 2 mg/kg, but convex at doses of 5 and 10 mg/kg. AP concentrations immediately after administration (C(p0)) were almost identical, irrespective of the dose received. The areas under the plasma concentration-time curves (AUCs) were proportional to the AP doses. At 2 mg/kg, the plasma total clearance (CL(tot)) of AP was high (279+/-80 mL/h), and its volume of distribution (Vd(ss)) was large (245+/-99 mL). Total blood clearance and time-averaged blood clearance (CL(ave)) values for AP were similar to those for R(+) propranolol (PL) after intravenous coadministration of R(+) PL (0.25 mg/kg) and AP (2 or 10 mg/kg). An in vitro serum protein binding study showed that the unbound fraction of AP was concentration-dependent. In guinea pigs pretreated with turpentine oil (2 mL/kg/day), the elimination of AP after intravenous doses of 2 and 5 mg/kg closely followed first-order kinetics, while C(p0) and AUC increased in proportion to the AP doses. The bound fraction of AP in the serum was larger after turpentine oil pretreatment than in normal guinea pig serum in vitro. From these observations, the nonlinear pharmacokinetics of AP observed in guinea pigs can be attributed to nonlinear serum protein binding.

journal_name

Drug Metab Pharmacokinet

journal_title

Drug metabolism and pharmacokinetics

authors

Shimizu M,Ohota T,Kishida M,Ogata H

doi

10.2133/dmpk.17.292

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

292-9

issue

4

eissn

1347-4367

issn

1880-0920

pii

JST.JSTAGE/dmpk/17.292

journal_volume

17

pub_type

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