Burger D M, Meenhorst P L, Mulder J W, Kraaijeveld C L, Koks C H, Bult A, Beijnen J H
Department of Pharmacy, Slotervaart Hospital, Amsterdam, The Netherlands.
Ther Drug Monit. 1994 Dec;16(6):616-20. doi: 10.1097/00007691-199412000-00015.
Serum phenytoin concentrations were investigated in 109 serum samples from 21 patients with the acquired immunodeficiency syndrome (AIDS) and in 1,231 serum samples from 557 control subjects during phenytoin therapy. Total phenytoin concentrations were significantly lower in patients with AIDS than in the reference population (8.8 +/- 0.7 mg/L (mean +/- SE) vs. 10.6 +/- 0.2 mg/L), although phenytoin doses were significantly higher in the AIDS patients. Body weight and the use of folic acid were negatively related to phenytoin concentrations, whereas use of clarithromycin resulted in higher phenytoin levels. Zidovudine did not influence phenytoin levels. Calculation of the Michaelis-Menten parameters showed that Vmax values were similar in seven human immunodeficiency virus (HIV)-infected patients as compared with 12 controls, but a nonsignificant trend of lower Km values in the HIV-positive group was observed. Measurement of free phenytoin concentrations demonstrated that the fraction of unbound drug was increased in patients with AIDS. Hypoalbuminemia was common in this population, which may complicate the interpretation of total phenytoin concentrations.
在苯妥英治疗期间，对21例获得性免疫缺陷综合征（AIDS）患者的109份血清样本以及557名对照受试者的1231份血清样本中的血清苯妥英浓度进行了研究。尽管AIDS患者的苯妥英剂量显著更高，但AIDS患者的总苯妥英浓度显著低于参考人群（8.8±0.7mg/L（均值±标准误）对10.6±0.2mg/L）。体重和叶酸的使用与苯妥英浓度呈负相关，而使用克拉霉素会导致苯妥英水平升高。齐多夫定不影响苯妥英水平。米氏参数的计算表明，与12名对照相比，7名人类免疫缺陷病毒（HIV）感染患者的Vmax值相似，但在HIV阳性组中观察到Km值有降低的不显著趋势。游离苯妥英浓度的测定表明，AIDS患者中未结合药物的比例增加。低白蛋白血症在该人群中很常见，这可能会使总苯妥英浓度的解释复杂化。
