de Moraes Natália Valadares, Lauretti Gabriela Rocha, Lanchote Vera Lucia
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Pharm Pharmacol. 2014 Sep;66(9):1222-30. doi: 10.1111/jphp.12255. Epub 2014 Apr 10.
The aim of this study was to evaluate the influence of poorly controlled type 1 (T1DM) and type 2 diabetes mellitus (T2DM) on the pharmacokinetics and metabolism of tramadol enantiomers in patients with neuropathic pain.
Nondiabetic patients (control group, n = 12), patients with T1DM (n = 9) or T2DM (n = 9), all with neuropathic pain and phenotyped as cytochrome P450 2D6 extensive metabolizers, received a single oral dose of 100 mg racemic tramadol. Serial blood samples were collected over a 24-h period.
Patients with T1DM showed reduced Cmax of both tramadol enantiomers. The plasma concentrations of the active (+)-M1 were significantly reduced in T1DM (area under the curve plasma concentration versus time (AUC∞ ): 313.1 ng·h/ml) when compared with nondiabetic patients (AUC∞ : 1246.6 ng·h/ml). The fraction unbound of (+)-M1 was increased in patients with T1DM. Patients with T1DM and T2DM showed reduced AUC and increased fraction unbound of (-)-M1.
The reduced total plasma concentrations of the active (+)-M1 in patients with T1DM may not be of clinical relevance because they are counterbalanced by the increased fraction unbound.
本研究旨在评估1型糖尿病（T1DM）和2型糖尿病（T2DM）控制不佳对神经性疼痛患者曲马多对映体药代动力学和代谢的影响。
非糖尿病患者（对照组，n = 12）、T1DM患者（n = 9）或T2DM患者（n = 9），均患有神经性疼痛且表型为细胞色素P450 2D6广泛代谢型，接受单次口服100 mg消旋曲马多。在24小时内采集系列血样。
T1DM患者的两种曲马多对映体的Cmax均降低。与非糖尿病患者相比，T1DM患者中活性（+）-M1的血浆浓度显著降低（血浆浓度-时间曲线下面积（AUC∞）：313.1 ng·h/ml），而非糖尿病患者的AUC∞为1246.6 ng·h/ml。T1DM患者中（+）-M1的未结合分数增加。T1DM和T2DM患者的（-）-M1的AUC降低且未结合分数增加。
T1DM患者中活性（+）-M1的总血浆浓度降低可能不具有临床相关性，因为未结合分数增加可起到平衡作用。
