Pharmacokinetics of intravenously administered meptazinol during general anaesthesia in man

The pharmacokinetics of meptazinol (3 mg kg-1 i.v.), a centrally acting opioid agonist-antagonist, were studied in six male and six female patients during anaesthesia with 1-3 vol.% enflurane and an infusion of 10-30 micrograms kg-1 min-1 etomidate. Arterial blood samples were taken up to 300 min postinjection. The plasma meptazinol concentrations, determined by HPLC, best fitted to a three-compartment open mamillary model with central elimination using a non-linear extended least-squares regression analysis. Derived pharmacokinetic parameters indicated a rapid distribution (T1/2 pi = 1.24 +/- 0.83 min, T1/2 alpha = 7.55 +/- 3.97 min), a short elimination half-life (T1/2 beta = 86.9 +/- 15.6 min), a volume of the central compartment twice as large in females (Vc = 0.557 +/- 0.237 l kg-1) as in males (Vc = 0.274 +/- 0.144 l kg-1), a small distribution volume at steady state (Vss = 2.52 +/- 0.66 l kg-1) and a high total plasma clearance (ClP = 1547 +/- 385 ml min-1). The elimination rate microconstant in females (k10 = 0.0577 +/- 0.0337 min-1) was significantly lower than in males (k10 = 0.1093 +/- 0.0437 min-1 with a lower drug fraction in the central compartment in the post-distributive phase (Fc = males: 0.08 +/- 0.02, females 0.19 +/- 0.11). As Vss and ClP were similar in both groups, sex-related differences were only observed in the dynamics of distribution of the drug. From a pharmacokinetic point of view we suspect that meptazinol shows very little cumulation on repeated i.v. administration as necessary during anaesthesia.