Pharmacokinetics of the new local anaesthetic N-[2-(2-Heptyloxyphenylcarbamoyloxy)ethyl]piperidinium chloride in rats and mice.

Pharmacokinetics of a local anaesthetic of the carbanilate type (Heptacaine; in the following briefly called HCP), was studied using a labelled product, N-[2-(2-[1-14C]-heptyloxyphenylcarbamoyloxy)ethyl]piperidinum++ + chloride. Determination of HCP in biological material was based on double extraction of HCP from alkaline media into n-heptane. The plasma concentration of HCP following i.v. administration to rats was approximated by a biexponential function. An open two-compartment pharmacokinetic model was conferred to the data. The model parameter estimates are as follows: terminal elimination half-life 3.80 +/- 0.15 h, distribution volume at steady state 9.31 l/kg, total body clearance 73.4 ml/min/kg, mean residence time 2.1 h. The systemic availability of the orally given HCP in solution was 35.8%. The HCP plasma AUC vs. dose relationship was linear within doses ranging from 2.78 to 4.33 mg/kg. The brain uptake index of HCP in comparison with 3H2O was 62.2%. Autoradiography in mice injected i.v. showed a heterogeneous distribution of the label in the tissues and its excretion by the urinary and biliary pathways. HCP showed strong affinity to the lung tissue. During 96 h after i.v. administration, 21% and 62% of the 14C dose was excreted into urine and faeces, respectively, and after oral administration, the excretion was 17% and 43%, respectively.