title: Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.
abstract: The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated curcumin, SD formulation enhanced the cellular uptake of rhodamine-123, a P-gp substrate by approximately 3 folds in NCI/ADR-RES cells. The oral and intravenous pharmacokinetics of saquinavir were also determined in rats with/without curcumin in the different formulations. Compared to the control given saquinavir alone, curcumin-loaded solid dispersion significantly (p<0.05) increased the oral exposure of saquinavir in rats, while it did not affect the intravenous pharmacokinetics of saquinavir. The AUC and Cmax of oral saquinavir increased by 3.8- and 2.7-folds, respectively in the presence of curcumin-loaded solid dispersion. In contrast, the untreated curcumin did not affect the oral pharmacokinetics of saquinavir. These results suggest that SD formulation of curcumin should be effective to improve the in vivo effectiveness of curcumin as an absorption enhancer, leading to the improved oral exposure of saquinavir.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Siksa-dong, Ilsan-Donggu, Goyang, Gyeonggi-do 410-820, Republic of Korea.
authors.forename: Su-A
authors.initials: SA
authors.lastname: Kim
authors.forename: Sung-Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Hoo-Kyun
authors.initials: HK
authors.lastname: Choi
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D019258:Saquinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013229:Stearic Acids / Q000737:chemistry; D013535:Suspensions
chemical_list: D017320:HIV Protease Inhibitors; D013229:Stearic Acids; D013535:Suspensions; D011092:Polyethylene Glycols; C067028:Solutol HS 15; D003474:Curcumin; D019258:Saquinavir
keywords: Bioavailability; Curcumin; P-gp; Saquinavir; Solid dispersion