Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers.

The pharmacokinetics and pharmacodynamics of prochlorperazine were studied in healthy volunteers using a recently developed h.p.l.c. assay. Eight subjects received 12.5 mg and 6.25 mg i.v. doses of prochlorperazine, a 25 mg oral dose and placebo in random order. Plasma half-life (t1/2) of prochlorperazine was 6.8 +/- 0.7 h and 6.9 +/- 0.8 h for the 12.5 mg and 6.25 mg i.v. doses respectively. Apparent volume of distribution and plasma clearance were high and the kinetics did not appear to be dose-related. Absorption of oral prochlorperazine appeared to be slow and bioavailability was very low. A metabolite, possibly prochlorperazine sulphoxide, was noted after oral dosing. Mild sedation was common after i.v. prochlorperazine, but cardiovascular effects were minimal. The main adverse effect was akathisia which was reported by five out of eight subjects after the higher i.v. dose. These results provide preliminary information on the pharmacokinetics of i.v. prochlorperazine which were previously unknown.