Effect of methanolic extract of Piper cubeba Linn. fruits on the pharmacokinetics of Pioglitazone in rats

Abstract

Herb-drug interaction about Oral antidiabetic drugs is a challenging concept. Present work was designed with an objective to investigate any possible pharmacokinetic effect of herbal drug Piper cubeba Linn.  on Pioglitazone, a commonly used antidiabetic agent. Since the MeOH-soluble fraction of the extract of Piper cubeba Linn fruit shows potent CYP3A4 inhibitory activity, it was speculated that the fruit extract may influence the bioavailability of Pioglitazone. In this experiment three groups (I, II & III) of Albino female wistar rats were used for pharmacokinetic study and the plasma levels were determined at various time points (0.5, 1, 2, 4, 8 and 24 h) by HPLC. The extract pretreatment increased AUC_0-∞ (bioavailability) of Pioglitazone after oral administration by 72.5% suggesting decreased metabolism, which could be due to inhibition of CYP3A4. In conclusion, add-on preparations containing this fruit extract may increase the bioavailability of Pioglitazone, with increased efficacy and/or adverse events and hence should be cautiously used.