Inhibitor of P-glycoprotein–mediated drug transport by curcumin in broiler chickens

Abstract

Abstract OBJECTIVE To investigate the role of curcumin in the regulation of P-glycoprotein (P-gp) and its influence on the pharmacokinetics of P-gp substrates. SAMPLE 39 broiler chicken and chicken embryonic primary hepatocytes. METHODS Chicken embryonic primary hepatocytes were treated with curcumin, after which cell viability, P-gp expression, and transport were assessed. Broiler chickens were pretreated with curcumin, after which P-gp expression and the pharmacokinetic behavior of orally administered sulfadiazine (a substrate of P-gp) were measured. RESULTS The preliminary results showed that the viability of chicken embryonic primary hepatocytes was enhanced by pretreatment with 40, 60, and 100 μM curcumin. Curcumin inhibits the expression and transport of P-gp. In vivo experiments showed that curcumin decreased the expression of P-gp in the broiler chicken liver, kidney, and small intestine. Pretreatment with curcumin changed the pharmacokinetic behavior of orally administered sulfadiazine by increasing the area under the curve (47.36 vs 70.35 h·mg/L, P < .01) and peak concentration (10.1 vs 14.53 μg/mL, P < .01). CLINICAL RELEVANCE Curcumin inhibited the expression and efflux of chicken P-gp, thereby improving the oral bioavailability of P-gp substrate drugs. These findings provide a rationale for exploiting herbal-drug interactions in veterinary practice to improve the absorption of drugs.