Pharmacokinetics of dixyrazine: low bioavailability, improved by food intake.

Abstract

The single-dose kinetics of the psychotropic phenothiazine dixyrazine was assessed in eight young healthy volunteers given the drug at three occasions: 10 mg intravenously, 25 mg orally in the fasting state, and 25 mg orally together with a standardized breakfast of 1,840 kJ. The plasma concentrations of dixyrazine were measured by high-pressure liquid chromatography. Like some other lipophilic weakly basic drugs, dixyrazine showed a rapid disappearance from plasma, having an elimination half-life of 3.4 h, a clearance of about 1,200 ml/min, and an apparent volume of distribution of 5.9 l/kg. Dixyrazine was found to have a very low and interindividually varying bioavailability; in the fasting state, dixyrazine bioavailability was only 1% in one subject, 3-6% in five others, and 11 and 24% in the remaining two subjects. The mean fasting bioavailability was 7.4%. After intake with breakfast, the mean bioavailability was increased to 12.4% (p less than 0.01), with a range of 2-29%. Probably, the low oral bioavailability is due to extensive presystemic (hepatic) degradation, and the food effect to a reduction of this process.