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Pharmacokinetic Comparison of a Slow‐Release Clonidine with a Conventional Formulation After Acute and Chronic Administration in Hypertensives
Author(s) -
Conway E. L.,
Anavekar S. N.,
Howes L. G.,
Louis W. J.
Publication year - 1992
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1992.tb03858.x
Subject(s) - cmax , pharmacokinetics , medicine , clonidine , pharmacology , microgram , anesthesia , chemistry , in vitro , biochemistry
The pharmacokinetic characteristics of a slow‐release formulation of clonidine (150 pg) were compared with those of a conventional formulation (75 μg) after acute and chronic (2 week) administration to 12 hypertensive subjects. The T max 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 T max 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 C max was approximately 60% lower for the slow‐release formulation (1 × 150 μg; 0.42 ± 0.09 ng/mL) compared with the conventional formulation (2 × 75 pg; 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 μg), the C max values were comparable: 1 × 150 pg‐0.99 ± 0.27 ng/mL, 1 × 75 pg‐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. T 1/2 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. T 1/2 was even longer for the slow‐release formulation after both acute and chronic dosing and was consistent with the continuing release of clonidine from the slow‐release product throughout the 48‐hour sampling time. The results confirm the slow‐release nature of the formulation and suggest that the elimination half‐life of clonidine does not correlate closely with the duration of the antihypertensive effect of the drug.