Hermida Jesús, Tutor J Carlos
Central Laboratory, University Hospital Clinic, Santiago de Compostela, Spain.
J Pharmacol Sci. 2005 Apr;97(4):489-93. doi: 10.1254/jphs.fpe04007x.
In patients with hypoalbuminemia, the total serum concentration of valproic acid may offer poor clinical information; however, very few clinical laboratories routinely analyze the free concentration of the drug. The aim of this study was to design a procedure to normalize the total concentration of valproic acid according to the level of serum albumin and using previously published free fraction values. In 121 adult patients, with albumin levels of 18 - 41 g/L, the total concentration of valproic acid was normalized using the derived equation: C(N) = alpha(H)C(H)/6.5, where alpha(H) is the free fraction of the drug corresponding to the patient's particular albuminemia and C(H) is the total concentration of valproic acid. The value of 6.5 corresponds to the free fraction of the drug for a serum albumin of 42 g/L (percentile 50 of the reference range). For total concentrations lower than 75 mg/L, the predicted normalized valproic acid concentrations were reasonably concordant with the observed normalized concentrations calculated using the data from a protein-binding study. In a significant number of cases, subtherapeutic concentrations of the drug became therapeutic and even supratherapeutic when corrected according to the albumin levels. Furthermore, cases with therapeutic drug concentrations frequently became supratherapeutic when normalized. The limitations and clinical applications of the proposed formula for normalizing the total concentration of valproic acid are presented. It is concluded that it may be useful for the posological management of hypoalbuminemic patients when the free concentration of the drug is not available, and decisions have to be made based on the total serum concentration.
在低白蛋白血症患者中，丙戊酸的血清总浓度可能无法提供良好的临床信息；然而，很少有临床实验室常规分析该药物的游离浓度。本研究的目的是设计一种程序，根据血清白蛋白水平并使用先前公布的游离分数值来标准化丙戊酸的总浓度。在121名白蛋白水平为18 - 41 g/L的成年患者中，使用推导公式C(N) = alpha(H)C(H)/6.5对丙戊酸的总浓度进行标准化，其中alpha(H)是对应于患者特定白蛋白血症的药物游离分数，C(H)是丙戊酸的总浓度。6.5这个值对应于血清白蛋白为42 g/L（参考范围的第50百分位数）时药物的游离分数。对于总浓度低于75 mg/L的情况，预测的标准化丙戊酸浓度与使用蛋白质结合研究数据计算出的观察到的标准化浓度合理一致。在大量病例中，根据白蛋白水平校正后，药物的亚治疗浓度变为治疗浓度甚至超治疗浓度。此外，治疗药物浓度的病例在标准化后经常变为超治疗浓度。本文介绍了用于标准化丙戊酸总浓度的建议公式的局限性和临床应用。得出的结论是，当无法获得药物的游离浓度且必须根据血清总浓度做出决策时，该公式可能对低白蛋白血症患者的剂量管理有用。
