Pharmacokinetic comparison of a slow-release clonidine with a conventional formulation after acute and chronic administration in hypertensives.

Abstract

The pharmacokinetic characteristics of a slow-release formulation of clonidine (150 micrograms) were compared with those of a conventional formulation (75 micrograms) after acute and chronic (2 week) administration to 12 hypertensive subjects. The Tmax of the slow-release formulation was significantly later than for the conventional formulation after both acute (8.3 +/- 6 hr vs. 2.1 +/- 2 hr) and chronic administration (4.0 +/- 3 hr vs. 2.5 +/- 2 hr). Although the Tmax did not change significantly with acute and chronic administration of the conventional preparation, it was significantly shorter after chronic administration of the slow-release formulation when acute and chronic administration were compared. The Cmax was approximately 60% lower for the slow-release formulation (1 x 150 micrograms; 0.42 +/- 0.09 ng/mL) compared with the conventional formulation (2 x 75 micrograms; 0.70 +/- 0.12 ng/mL) after acute administration, whereas in the steady state, in which the dose of the conventional preparation was halved (75 micrograms), the Cmax values were comparable: 1 x 150 micrograms-0.99 +/- 0.27 ng/mL, 1 x 75 micrograms-0.84 +/- 0.20 ng/mL and the dose-normalized interdose AUC were identical for the conventional (16.2 +/- 4.3 ng/mL.hr) and slow release (16.6 +/- 5.3 ng/mL.hr) products. T1/2 values for the conventional formulation of clonidine exceeded 20 hours in all but one subject and were considerably longer than those in previous reports, including those of the authors, in which a less sensitive assay was used.(ABSTRACT TRUNCATED AT 250 WORDS)