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.
Scasnár
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V
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Kállay
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Z
Bezek
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S
Trnovec
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T
Durisovă
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M
D000284:Administration, Oral; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D005243:Feces / Q000032:analysis; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D010880:Piperidines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
D000779:Anesthetics, Local; D010880:Piperidines; C013549:heptacaine