alexa In vitro and in vivo evaluation of the effects of duloxetine on P-gp function.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Ruike Z, Junhua C, Wenxing P

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Abstract OBJECTIVE: To evaluate the effect of duloxetine (DLX) on the P-glycoprotein (P-gp) function in vitro and in vivo. METHOD: In vitro experiment was conducted using the Caco-2 cell, a human colon cancer cell line that naturally expresses the P-gp and P-gp function was evaluated by monitoring whether DLX affect the accumulation of Rhd123. In vivo study was conducted by quantitating the effect of orally administered DLX on the bioavailability of talinolol. RESULTS: In the in vitro study, incubation of Caco-2 cell with DLX caused a concentration-dependent increase in the accumulation of Rhd123. In the in vivo study, co-administration of DLX increased the bioavailability of talinolol. The ratio (90\% confidence intervals) of AUC(0-60), AUC(0-∞), and C(max) (talinolol alone versus talinolol plus DLX) were 0.87(0.77-1.06), 0.85(0.74-1.01), 0.87 (0.68-1.12). CONCLUSION: Our results suggest that DLX could inhibit the function of P-gp in vitro and in vivo, and caution should be exercised when DLX is to be co-administered with drugs that are P-gp substrate. Copyright © 2011 John Wiley & Sons, Ltd. This article was published in Hum Psychopharmacol and referenced in Journal of Bioequivalence & Bioavailability

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