Role of hepatic blood flow and metabolism in the pharmacokinetics of ten drugs in lean, aged and obese rats.

Autor: Subramanian, Murali, Kurawattimath, Vishwanath, Pocha, Krishna, Freeden, Chris, Rao, Indranil, Thanga Mariappan, T., Marathe, Punit H., Vikramadithyan, Reeba K., Abraham, Pamela, Kulkarni, Chetan P., Katnapally, Prasanna, Nutakki, Ravikumar, Paruchury, Sundeep, Bhutani, Priyadeep, Mandlekar, Sandhya
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Zdroj: Xenobiotica; Dec2014, Vol. 44 Issue 12, p1108-1116, 9p
Abstrakt: 1. The effect of age and obesity on the pharmacokinetics (PK), hepatic blood flow (HBF) and liver metabolism of 10 compounds was determined in rats. The animals fed a high-fat diet were defined as the diet-induced obese (DIO) group, while the animals that were aged similar to the DIO rats but not fed with high-fat diet were called the age-matched (AM) group. 2. The clearance (CL) values of high CL compounds (CL > 50 mL/min/kg, namely propranolol, diazepam, phenytoin, ethinylestradiol, lorcaserin and fenfluramine) decreased significantly (1.5- to 6-fold) in DIO and AM rats as compared to lean rats, while there was no clear trend for change in CL for the low-to-moderate CL compounds (CL < 50 mL/min/kg, namely atenolol, chlorzoxazone, vancomycin and sibutramine). Hepatocytes incubations revealed a change in half life ( t1/2) only for phenytoin. The body weight normalized liver weights and HBF of AM and DIO rats were found to be 2- to 3-fold lower than in lean rats. 3. Our findings suggest that age, and diet to a lesser extent, can reduce HBF and body normalized liver weights and, hence, also reduce CL values for high CL compounds in rats. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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