Pioglitazone: effect on CYP3A4 activity.
Article Details
- CitationCopy to clipboard
Nowak SN, Edwards DJ, Clarke A, Anderson GD, Jaber LA
Pioglitazone: effect on CYP3A4 activity.
J Clin Pharmacol. 2002 Dec;42(12):1299-302.
- PubMed ID
- 12463723 [ View in PubMed]
- Abstract
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-beta-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-beta-hydroxycortisol/cortisol ratio. The mean +/- SD 6-beta-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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Pioglitazone Cytochrome P450 3A4 Protein Humans UnknownSubstrateInducerDetails