Pharmacokinetics of nocloprost in human volunteers and its relation to dose

Summary

The pharmacokinetics and absolute bioavailability of nocloprost, a synthetic PGE₂-analogue with cytoprotective properties, was investigated in human volunteers as a function of the dose. Ten young male volunteers received nocloprost 5 μg i. v. and 100, 200 and 400 μg p.o. in random order at weekly intervals. Serum nocloprost levels were monitored for up to 12 h after each dose, using a specific, validated assay.

After nocloprost 5 μg i. v. the highest serum level of 373 pg·ml⁻¹ was found in the first sample 5 min after injection, and the subsequent decline showed one or two phases, with half-lives of 4 and 49 min. The AUC was 89 pg·h·ml⁻¹, the total plasma clearance was 13.2 ml·min⁻¹·kg⁻¹, and the volume of distribution at steady state was 0.16 l·kg⁻¹.

After oral administration the maximum serum level and AUC increased in proportion to the dose. t_max showed a wide scatter, with an average value of about 30 min independent of the dose. Although not detectable in every subject, post maximum serum levels declined biphasically, with half-lives of ca 10 and 35–40 min.

The absolute bioavailability after oral administration averaged about 2% and was independent of the dose.