The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.