Enhancing effect of -Lactoglobulin on the rate of Cyclosporin absorption

1Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Rajadhevi, Bangkok 10400, Thailand 2Division of Pharmacokinetics and Pharmacodynamics, Department of Therapeutic Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, 142-8555, Japan A b s t r a c t The aim of this study was to determine the effects of β-lactoglobulin (β-LG) on the intestinal absorption of cyclosporin A (CsA) in vivo and in vitro. After intraduodenal co-administration of CsA (5 mg/kg) with 150 mg/kg β-LG, Tmax was significantly lower than that of control rats which were given the same dose of CsA without β-LG. Cmax and AUC were significantly increased as compared with the control while T1/2 were not significant. Moreover, a deconvolution method revealed that the rate of CsA absorption was enhanced by β-LG (150 mg/kg) by about 12 times. These results indicate that β-LG significantly enhanced the rate of CsA absorption and the extent of CsA bioavailability in the gut. β-LG did not change the solubility of CsA in vitro, but β-LG increased the apical-tobasolateral permeability clearance of CsA (PScell), with pronounced increase in the permeability of unbound CsA (PSu,cell), across the Caco-2 monolayers in a concentration-dependent manner in vitro. It was thus considered that β-LG-mediated transport of CsA might be a possible mechanism to enhance the intestinal absorption of CsA in vivo.