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Makhova A.A.,Moscow Medical Academy | Shumyantseva V.V.,Russian Academy of Medical Sciences | Shich E.V.,Moscow Medical Academy | Bulko T.V.,Russian Academy of Medical Sciences | And 5 more authors.
BioNanoScience | Year: 2011

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. © 2011 Springer Science+Business Media, LLC.


Shumyantseva V.V.,Russian Academy of Medical Sciences | Shich E.V.,Moscow Medical Academy | Machova A.A.,Moscow Medical Academy | Bulko T.V.,Russian Academy of Medical Sciences | And 5 more authors.
Biomeditsinskaya Khimiya | Year: 2011

It was shown that vitamin B group permit to shorten the longitude of diclofenak therapy and to reduce the daytime dose of this drug. All three schemes of diclofenac treatment - only diclofenac, diclofenac plus 2 tablets of Gitagamp (mixture of vitamin B group), and diclofenac plus 4 tablets of Gitagamp - gave maximum value of diclofenal in blood through 1 hour after treatment. In the case of diclofenak treatment without vitamins Cmax corresponds to 1137.2±82.4 ng/ml, with 2 tablets of Gitagamp - Cmax 1326.7±122.5 ng/ml, and with 4 tablets - Cmax 2200.4±111.3 ng/ml. Positive influence of vitamin B group on the decrease of pain syndrome was shown. Pharmacodynamics and pharmacokinetics data were confirmed in electrochemical experiments with cytochrome P450 3A4. For enzyme immobilization screen printed graphite electrodes modified with gold nanoparticles and synthetic membrane-like compound didodecyldimethylammonium bromide (DDAB/Au) were used. Electrochemical analysis reviled the influence of vitamin B group on metabolism of non steroid anti inflammation drug diclofenac catalyzed by cytochrome P450 3A4. Riboflavin was the most effective inhibitor of diclofenac hydroxylation by cytochrome P450 3A4 as was compared at 300 M concentration of vitamin B group (B1, B2, B6). These data confirmed the opportunity of pharmacokinetic parameters regulation and the level of pharmacodynamic effects by the influence of vitamin B group on the catalytic activity of cytochrome P450 3 A4.


Shumyantseva V.V.,Russian Academy of Medical Sciences | Shich E.V.,Moscow State University | Machova A.A.,Moscow State University | Bulko T.V.,Russian Academy of Medical Sciences | And 5 more authors.
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry | Year: 2012

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 (B 1, B 2, and B 6) 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. © Pleiades Publishing, Ltd., 2012.

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