Circadian Changes In Drugs Metabolism

Hepatic drug metabolism is generally assumed to depend on liver enzyme activity and / or hepatic blood flow both have been shown to be circadian time-dependent.

Circadian variation in enzyme activity were documented in the liver, kidney and brain . However, these data were obtained in animals and no direct data on enzyme activity have been reported in humans. Circadian variations in hepatic blood flow induced changes in liver perfusion and, thus, temporal variations in the clearance of such drugs.

Diurnal variations have been reported for several microsomal drug metabolism activities mediated by the cytochrome p-450 mixed function oxidase systems . The oxidative reaction catalysed by the cyctochrome p-450 monooxygenase system are the major pathways involved in the disposition of drugs and toxic chemical agents. Hence, any chronobiological variations, in the rate of these processes may modify the pharmacokinetics of drugs whose body clearance is directly related to hepatic velocity of oxidative reactions. Also as these biotransformations are responsible for the first pass elimination of drugs the bioavailability of drugs subjected to first pass effect may get affected by the time dependent variations of these liver processes.