The influence of B-group vitamins on monooxygenase activity of cytochrome P450 3A4: Pharmacokinetics and electro analysis of the catalytic properties

Abstract

Simultaneous administration of loading doses of B-group vitamins and diclofenac allow to decrease the daily dose of this drug without reduction of its analgesic effect. In all three schemes of the diclofenac intake (diclofenac alone, diclofenac plus 2 tablets of Gitagamp (a mixture of B-group vitamins), and diclofenac plus 4 tablets of Gitagamp—maximal concentration of blood diclofenal (C_max) was observed 1 h after the treatment. In the case of diclofenac treatment alone, with 2 tablets of Gitagamp, and with 4 tablets of Gitagamp C_max values were 1137.2 ± 82.4, 1326.7 ± 122.5 and 2200.4 ± 111.3 ng/mL, respectively. Thus, loading doses of B-group vitamins caused a statistically significant effect on the C_max value of blood diclofenac concentration; they also reduced manifestations of the pain syndrome. Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical studies of cytochrome P450 3A4 (CYP3A4) activity. This enzyme was immobilized onto screen printed graphite electrodes modified with gold nanoparticles and synthetic membrane-like compound didodecyldimethylammonium bromide (DDAB/Au). Electrochemical analysis revealed the influence of B-group vitamins on metabolism of the non-steroidal anti-inflammatory drug diclofenac catalyzed by cytochrome P450 3A4. Comparative analysis of the effect of 300 μM vitamins of the B-group (B₁, B₂, and B₆) demonstrated that riboflavin was the most effective inhibitor of diclofenac hydroxylation catalyzed by CYP3A4. These data support possibility of regulation of pharmacokinetic parameters and manifestation of pharmacodynamic effects by loading doses of B-group vitamins, which regulate the catalytic activity of drug metabolizing enzymes such as cytochrome P450 3A4.