Titre du document / Document title

Effect of gemfibrozil on the pharmacokinetics of pioglitazone

Auteur(s) / Author(s)

DENG Li-Jing ^{(1 2)} ; FENG WANG ⁽¹⁾ ; LI Huan-De ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, The Central South University, Changsha, 410011, CHINE
⁽²⁾ Clinical Pharmaceutical Institute, Pharmaceutical Department, The First Affiliated Hospital of Nanhua University, Hengyang, CHINE

Résumé / Abstract

Objective: Our objective was to study the effects of gemfibrozil on the pharmacokinetics of pioglitazone and the active compounds, which are all the substrates of CYP2C8 and CYP3A4. Methods: In a randomized, two-phase crossover study, 10 healthy volunteers were pretreated for 2 days with either 600 mg oral gemfibrozil or placebo twice daily. On day 3, they received a single dose of 600 mg gemfibrozil or placebo, and 1 h later they received a single oral dose of 30 mg pioglitazone. Plasma concentrations of pioglitazone and both active metabolites M-III and M-IV were measured for up to 120 h. Results: Gemfibrozil raised the mean total area under the concentration-time curve (AUC) of parent pioglitazone 3.4-fold (P<0.001). No statistically significant changes were seen in the total AUC of M-III or M-IV after gemfibrozil pretreatment. Gemfibrozil reduced the M-III/pioglitazone and M-IV/pioglitazone AUC_0-∞ ratio by 71% (P<0.001) and 65%(P<0.001), strikingly prolonging their t₁/2. Conclusion: Gemfibrozil greatly increased the plasma concentration of parent pioglitazone and also inhibited the further metabolism of M-III and M-IV. Careful blood glucose monitoring and dosage adjustments are suggested during coadministration of pioglitazone and gemfibrozil.

Revue / Journal Title

European journal of clinical pharmacology   ISSN 0031-6970 

Source / Source

2005, vol. 61, n^o11, pp. 831-836 [6 page(s) (article)] (15 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1970) (Revue)

Mots-clés anglais / English Keywords

Thiazolidinedione derivatives ; Fibrate derivatives ; Hypoglycemic agent ; Antilipemic agent ; Human ; Inhibitor ; Pioglitazone ; Pharmacokinetics ; Gemfibrozil ;

Mots-clés français / French Keywords

Thiazolidinedione dérivé ; Fibrate dérivé ; Hypoglycémiant ; Hypolipémiant ; Homme ; Inhibiteur ; Pioglitazone ; Pharmacocinétique ; Gemfibrozil ;

Mots-clés espagnols / Spanish Keywords

Tiazolidinediona derivado ; Fibrato derivado ; Hipoglicemiante ; Hipolipemiante ; Hombre ; Inhibidor ; Pioglitazona ; Farmacocinética ; Gemfibrozilo ;

Mots-clés d'auteur / Author Keywords

Gemfibrozil ; Pioglitazone ; Pharmacokinetic ; Inhibit ;

Localisation / Location

INIST-CNRS, Cote INIST : 13739, 35400013444998.0060