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Pioglitazone: Effect on CYP3A4 Activity
Author(s) -
Nowak Sandra N.,
Edwards David J.,
Clarke Anthony,
Anderson Gail D.,
Jaber Linda A.
Publication year - 2002
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 - 10.1177/0091270002042012009
Subject(s) - pioglitazone , cyp3a4 , pharmacokinetics , medicine , urine , thiazolidinedione , pharmacology , endocrinology , urology , metabolism , diabetes mellitus , cytochrome p450 , type 2 diabetes
Clinical studies demonstrate CYP3A4 enzyme induction with troglitazone, a thiazolidinedione derivative structurally related to pioglitazone. The objective of this prospective, open‐label study conducted in healthy volunteers was to evaluate the influence of multiple‐dose pioglitazone therapy on the urinary excretion ratio of 6‐β‐hydroxycortisol to cortisol, an endogenous marker of CYP3A4 activity. Twelve subjects were given pioglitazone hydrochloride 45 mg daily for 14 days. Urine was collected over a 24‐hour period before pioglitazone and after administration of the last tablet. Baseline and posttreatment CYP3A4 activity was assessed with the urinary 6‐β‐hydroxycortisol/cortisol ratio. The mean ± SD 6‐β hydroxycortisol/cortisol ratios before and after treatment were 8.3 ± 4.4 and 9.4 ± 4.0, respectively (p = 0.29). The mean change from baseline was a nonsignificant 20.2%. Nine subjects had a small increase and 3 subjects had a reduction in the ratio. Using the ratio as a marker of CYP3A4 activity, the data support a lack of inductive effect on CYP3A4 by multiple‐dose pioglitazone therapy. Thus, administration of pioglitazone should not result in clinically significant effects on the pharmacokinetics of other CYP3A4 substrates.