Shumiantseva V V, Shikh E V, Makhova A A, Bylko T V, Kukes V G, Sizova O S, Ramenskaia G V, Usanov S A, Archakov A I
Biomed Khim. 2011 May-Jun;57(3):343-54. doi: 10.18097/pbmc20115703343.
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 3A4.
结果表明,B族维生素可缩短双氯芬酸治疗疗程,并降低该药的日间剂量。双氯芬酸的三种治疗方案——单用双氯芬酸、双氯芬酸加2片Gitagamp(B族维生素混合物)以及双氯芬酸加4片Gitagamp——在治疗后1小时血中双氯芬酸达到最大值。在不使用维生素进行双氯芬酸治疗的情况下,Cmax为1137.2±82.4 ng/ml,加2片Gitagamp时Cmax为1326.7±122.5 ng/ml,加4片时Cmax为2200.4±111.3 ng/ml。研究显示B族维生素对疼痛综合征的减轻有积极影响。在细胞色素P450 3A4的电化学实验中证实了药效学和药代动力学数据。为进行酶固定化,使用了用金纳米颗粒和合成膜状化合物二癸基二甲基溴化铵(DDAB/Au)修饰的丝网印刷石墨电极。电化学分析揭示了B族维生素对细胞色素P450 3A4催化的非甾体抗炎药双氯芬酸代谢的影响。在300 μM浓度的B族维生素(B1、B2、B6)中,核黄素是细胞色素P450 3A4催化双氯芬酸羟基化的最有效抑制剂。这些数据证实了通过B族维生素对细胞色素P450 3A4催化活性的影响来调节药代动力学参数和药效学效应水平的可能性。