THE HEPATIC CYP3A4 UPREGULATED INCREASED METABOLISM IN RESPONSE TO PHYSICAL ACTIVITY AT HIGH ALTITUDEAbstract
The present study was designed to assess the pharmacokinetics of drug metabolized by hepatic cytochrome 3A4 (CYP3A4) in human volunteers with physical activity at the high altitude hypobaric hypoxic environment. The International Physical Activity Questionnaire short form 7 (IPAQ SF-7) was used to measure the physical activity. The total of 24 healthy male volunteers participated in this study; for them, the intensity of physical activity was measured in terms of metabolic equivalence of tasks (METs). The pharmacokinetic study was conducted using an oral dose of Alprazolam. The blood samples were collected at fixed intervals up to 24 h. The pharmacokinetic variables were found to be changed with increased intensity of physical activity. The metabolism phase was significantly decreased in vigorous and walking physical activity groups. The area under the curve (AUC) and half-life were also decreased. The pharmacokinetics of drug was found to be decreased with increased intensity of vigorous and walking physical activity in humans working at high altitude hypobaric hypoxia environment. It was assumed that oxygenation of blood and blood flow to the liver was decreased in response to hypobaric hypoxia environment; thought to cause hepatic CYP3A4 dysregulation, resulting in increased metabolism and faster elimination of the drug.
A. Thomas *, M. K. Samanta, R. Chauhan, S. P. Jose, J. B. Moktan and N. B. Sridharamurthy
Department of Pharmacy Practice, Oxbridge College of Pharmacy, Bangalore, Karnataka, India.
12 October 2018
02 February 2019
28 February 2019
01 July 2019