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Steady‐State Pharmacokinetics and Dose Proportionality of Troglitazone and Its Metabolites
Author(s) -
Loi ChoMing,
Alvey Christine W.,
Vassos Artemios B.,
Randinitis Edward J.,
Sedman Allen J.,
Koup Jeffrey R.
Publication year - 1999
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 - 10.1177/00912709922008533
Subject(s) - troglitazone , metabolite , pharmacokinetics , pharmacology , chemistry , active metabolite , dosing , steady state (chemistry) , medicine , biochemistry , peroxisome , gene
This study evaluated the steady‐state pharmacokinetics and dose proportionality of troglitazone, metabolite 1 (sulfate conjugate), and metabolite 3 (quinone metabolite) following administration of daily oral doses of 200, 400, and 600 mg troglitazone for 7 days (per dosing period) to 21 subjects. During each dosing period, plasma samples were collected predose on days 1, 5, 6, and 7 and serially for 24 hours on day 7. Steady‐state plasma concentrations for troglitazone, metabolite 1, and metabolite 3 were achieved by day 7. Troglitazone was rapidly absorbed with mean t max values of 2.7 to 2.9 hours. Mean C max and AUC (0–24) values for troglitazone, metabolite 1, and metabolite 3 increased proportionally with increasing troglitazone doses over the clinical dose range of 200 mg to 600 mg administered once daily. Mean troglitazone CL/F, percent fluctuation, and AUC ratios of metabolite 1 and metabolite 3 to troglitazone were similar across dose groups. These data suggest that the pharmacokinetics and disposition of troglitazone and its metabolites are independent of dose over the dose range studied. Thus, troglitazone, metabolite 1, and metabolite 3 displayed linear pharmacokinetics at steady‐state .