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Pharmacokinetics of Clentiazem After Intravenous and Oral Administration in Healthy Subjects
Author(s) -
Shah Ajit K.,
Bhargava Vijay O.,
Weir Scott J.,
Giesing Dennis H.
Publication year - 1993
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.1552-4604.1993.tb04669.x
Subject(s) - pharmacokinetics , volume of distribution , cmax , bioavailability , oral administration , crossover study , medicine , half life , intravenous bolus , bolus (digestion) , pharmacology , anesthesia , placebo , alternative medicine , pathology
This study characterized the pharmacokinetics of clentiazem (CLZ) after a single intravenous bolus (IV) and oral (PO) dose in humans. Twenty‐four healthy male subjects (28.5 ± 5.2 years; 77 ± 8.2 kg) received IV (20 mg) and PO (80 mg) doses of CLZ as part of a four‐way, randomized, complete crossover study. Serial blood samples were drawn up to 48 hours after administration of the drug. Plasma samples were analyzed for CLZ and three metabolites by a high‐pressure liquid chromatography method. The values (mean [CV,%])/or systemic clearance, volume of distribution at steady‐state, and half‐life of CLZ were 63.6 L/hour (23.5), 756.1 L (19.1), and 10.6 hours (33.1), respectively, after IV administration. The peak plasma CLZ concentration (Cmax) and time to Cmax were 37.0 ng/mL (38.7) and 3.7 hours (22.9), respectively, with a lag time after PO administration. The absolute bioavailability of PO CLZ was 45% (30.7). The ratio of area under the curve of N‐desmethyl CLZ to that of CLZ increased from 0.15 (57.0) after IV to 0.60 (21.4) after PO administration, suggesting a significant first‐pass effect. The mean residence time and mean absorption time of CLZ were 12.3 hours (24.3) and 3.1 hours (88.1), respectively. The plasma concentration‐time data of CLZ can be described by either a one‐ or two‐compartment pharmacokinetic model.