Pharmacokinetics and metabolism of the anti-arrhythmic carocainide in man

Abstract

1. The pharmacokinetics and metabolism of the anti-arrhythmic drug carocainide have been investigated in six healthy adult volunteers following single 100 mg intravenous and oral doses. Carocainide was labelled with ¹⁴C in the benzofuran ring.

2. After i.v. administration, plasma concentration/time decay of carocainide was triexponential. Mean plasma elimination half-life of the drug was 5·0 · 2·2 h (i.v.) and 5·4 · 1·1 h (p.o.). Carocainide was virtually completely absorbed after the oral dose. The drug was eliminated mostly as unchanged drug in urine by the two routes of administration. There was some evidence that carocainide underwent enterohepatic cycling.

3. Binding of carocainide to plasma proteins was saturable although not in the concentration range found in vivo. The drug was bound almost entirely to the a α₁-acid glycoprotein fraction, to one class of binding sites with a moderate affinity constant

4. Metabolism of carocainide, a secondary elimination process, occurred by oxidative cleavage of the benzofuran ring and by N-oxidation of the pyrrolidine ring.