Effect of Cellgevity® Supplement on Selected Rat Liver Cytochrome P450 Enzyme Activity and Pharmacokinetic Parameters of Carbamazepine

Abstract

Background: There is considerable evidence that many patients concurrently administer dietary supplements with conventional drugs, creating a risk for potential drug-supplement interaction. The aim of this study was to determine the effect of Cellgevity® supplement on selected rat liver cytochrome P450 (CYP) enzymes. Also, we sought to deternine the effect of Cellgevity® on the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Methods: Male Sprague-Dawley (SD) rats were randomly put into 5 groups and administered (per os) either distilled water (negative control), Cellgevity® (3 separate doses) or phenobarbital (positive control). Modulation of liver CYP enzyme activity was evaluated after 30 days of treatment, using probe substrates, spectroscopic and high-performance liquid chromatographic methods. In the pharmacokinetic study, 12 SD rats were divided into 2 groups administered (per os) carbamazepine plus Cellgevity®, or carbamazepine plus normal saline, both over a period of 14 days. Blood samples from rats in the same group were collected after treatment. Serum samples were prepared and pooled together at each specific sampling time point. Levels of carbamazepine were determined using a fluorescence polarization immunoassay. Results: Activities of rat liver CYP1A1/2, CYP2C9 and CYP2D6 were significantly increased by Cellgevity® after 30-day treament. Pharmacokinetic parameters for rats administered carbamazepine with Cellgevity® vis-a-vis carbamazepine with normal saline were as follows: Cmax; 20 μmol/L vs 11 μmol/L, AUC0→24; 347 μmol.h/L vs 170 μmol.h/L, Ke; 0.28 h-1 vs 0.41 h-1, and t1/2; 2.3 h vs 1.7 h, respectively.Conclusions: Cellgevity® increased the activity of rat CYP1A1/2, CYP2C9 and CYP2D6 enzymes, and altered the pharmacokinetics of carbamazepine in rats.