Pharmaceutical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2012 Mar;15(2):702-8.
As there are conflicting findings regarding the clearance-dose and patient characteristics relationships for valproic acid (VPA), this study was conducted to investigate the relationship between patient demographic characteristics, VPA dosage and the drug clearance in adult Iranian patients.
Patients (N= 47) were either on monotherapy with VPA or were under co-treatment with drugs that have no effect on VPA pharmacokinetic (PK) profile. All of the patients received VPA at therapeutic dose. Steady state trough plasma concentrations of VPA were determined by Fluorescence Polarization Immunoassay (FPIA) and VPA apparent clearance (CL/F) were calculated in each patient.
Mean VPA dose and VPA CL/F were 8.93±2.2 mg/kg/day and 0.65±0.55 l/hr respectively. No significant correlations were found between VPA CL/F and patients' age, TBW and VPA dose. VPA CL/F values of male and female patients were compared and no significant difference between these two groups was noted (P> 0.05). Significant correlation between VPA dose and total trough plasma concentration was found (P= 0.001). Mean total VPA plasma concentration was 54.51±23.74 mg/l.
Our study showed PK of VPA was not affected by age, sex, TBW and VPA dose. However, for detailed results and construction of VPA PK model in Iranian patients, it is necessary to evaluate VPA PK in a larger sample size with different VPA doses, age and TBW ranges.
由于有关丙戊酸(VPA)清除剂量与患者特征的关系存在相互矛盾的发现,因此进行了这项研究,以调查伊朗成年患者的人口统计学特征、VPA 剂量与药物清除率之间的关系。
患者(N=47)要么接受 VPA 单药治疗,要么接受对 VPA 药代动力学(PK)特征无影响的药物联合治疗。所有患者均接受治疗剂量的 VPA。通过荧光偏振免疫测定法(FPIA)测定稳态谷血浆 VPA 浓度,并计算每位患者的 VPA 表观清除率(CL/F)。
VPA 平均剂量和 VPA CL/F 分别为 8.93±2.2mg/kg/天和 0.65±0.55l/hr。VPA CL/F 与患者年龄、TBW 和 VPA 剂量之间无显著相关性。比较了男性和女性患者的 VPA CL/F 值,两组之间无显著差异(P>0.05)。发现 VPA 剂量与总谷血浆浓度之间存在显著相关性(P=0.001)。平均总 VPA 血浆浓度为 54.51±23.74mg/l。
我们的研究表明,VPA 的 PK 不受年龄、性别、TBW 和 VPA 剂量的影响。然而,为了获得伊朗患者更详细的结果和构建 VPA PK 模型,有必要在更大的样本量、不同的 VPA 剂量、年龄和 TBW 范围内评估 VPA PK。