Electroanalysis of Cytochrome P450 3a4 Catalytic Properties with Nanostructured Electrodes: the Influence of Vitamin B Group on Diclofenac Metabolism

Application of vitamin B group permits to shorten the longitude of diclofenac (DF) therapy and to reduce the daytime dose of this drug. All the three schemes of treatment with diclofenac—i.e., diclofenac alone, diclofenac plus two tablets of Gitagamp (composition of vitamin B group), and diclofenac plus four tablets of Gitagamp—enabled to achieve maximum diclofenac concentration in blood within 1 h after its uptake. In the case of diclofenac administration, C max corresponds to 1,137.2 ± 82.4 ng/ml (3.41 ± 0.25 μM); with two tablets of Gitagamp, it corresponds to 1,326.7 ± 122.5 ng/ml (3.97 ± 0.37 μM), and with four tablets, it corresponds to 2,200.4 ± 111.3 ng/ml (6.59 ± 0.33 μM). Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical experiments with cytochrome P450 3A4 and electrodes nanostructured with gold nanoparticles, stabilized by the synthetic membrane-like surfactant didodecyldimethylammonium bromide. Electrochemical analysis revealed the influence of vitamin B group on the metabolism of the nonsteroidal anti-inflammatory drug diclofenac catalyzed by cytochrome P450 3A4. Riboflavin was found to be the most effective inhibitor of diclofenac hydroxylation by cytochrome P450 3A4, as was demonstrated by comparing the influence of vitamin B group (B1, B2, and B6) at the same (300 μM) concentration. The data obtained provide evidence for the possible regulation of pharmacokinetic parameters and pharmacodynamic effects for DF through the influence of vitamin B group on the catalytic activity of cytochrome P450 3A4.