ABSTRACT
Results:
7-ethoxycoumarin O-deethylase and 7-ethoxyresorufin O-deethylase activities of the control and the phenobarbital groups displayed significant daily rhytmic variations. However, ethylmorphine N-demethylase activities in the control and the phenobarbital groups did not show any circadian rhythm
Conclusion:
The daily rhytmic variations in the microsomal enzyme activities which have a role on drug metabolism may affect the pharmacokinetics depen-ding on the time of the day of the drug intake. This situation may lead to the variations on the drug effectiveness.
Materials and Methods
In this study the male rats (weighting between 200-250 g) which were synchronised by 12h light (0800-2000h) and 12h dark (2000-0800h) cycle were used. The rats were randomly divided into two groups and as the phenobarbital and the control. The rats in the phenobarbital group were injected with a single dose of phenobarbital (75 mg/kg/day, 10 ml/kg, i.p.) for 4 successive days in order to induce the enzyme activities. The cont-rol group received 0.9% saline injections simultaneously. The rats were killed by cervical dislocation at six different time points of the day (0900, 1300, 1700, 2100, 0100, 0500) and the liver specimens were homogenized to obtain the post-mitochondrial supernatant fractions. The N-demethylase activity was measured by Hantysch reaction whereas the O-deethylase was measured fluorometrically through 7-hydroxycoumarin and the resorufin
Purpose:
The activities of the enzyme systems which take part in the drug biotransformation is known to exhibit daily variations as a result of the bi-ological rhytms and this situation may alter the drug pharmacokinetics de-pending on the drug taking time. However there is not any publication indi-cating how the enzyme induction mechanisms affect the activity rhytms. In this study it was aimed to investigate the daily rhytmic variations in the acti-vities of some hepatic microsomal drug metabolizing enzymes, namely ethyl-morphine N-demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase, with phenobarbital induction.