Cramer J A, Mattson R H, Bennett D M, Swick C T
Ther Drug Monit. 1986;8(4):411-5. doi: 10.1097/00007691-198612000-00005.
Total and free valproic acid (VPA) serum concentrations differ between patients on sole therapy (SOLE Group) and those taking multiple drugs (MULTI Group). We found significantly higher total and free VPA levels and free fractions in 25 SOLE patients than in 29 MULTI patients, both at morning predose (minimum) and postdose (maximum) testing. Results in SOLE versus MULTI patients were, respectively, as follows: total minimum 70.5 vs. 50.2 micrograms/ml (p less than 0.01); total maximum 106.8 vs. 89.5 micrograms/ml (p less than 0.05); free minimum 9.8 vs. 4.4 micrograms/ml (p less than 0.001); free maximum 18.9 vs. 12.0 micrograms/ml (p less than 0.01). The wide variation in total and free levels suggests the need to monitor VPA levels carefully. Not only does use of other drugs influence VPA kinetics, but the time since last dose also affects levels. Nonlinear binding causes large increases in free levels as total VPA concentration rises. We monitor free and total VPA at minimum and maximum along with evaluation of side effects and seizures for better interpretation of dosage requirements.
单独治疗患者（单药组）和联合用药患者（多药组）的丙戊酸（VPA）血清总浓度和游离浓度存在差异。我们发现，在清晨给药前（最低值）和给药后（最高值）检测时，25名单药组患者的VPA总浓度和游离浓度以及游离分数均显著高于29名多药组患者。单药组与多药组患者的检测结果分别如下：总浓度最低值为70.5 vs. 50.2微克/毫升（p<0.01）；总浓度最高值为106.8 vs. 89.5微克/毫升（p<0.05）；游离浓度最低值为9.8 vs. 4.4微克/毫升（p<0.001）；游离浓度最高值为18.9 vs. 12.0微克/毫升（p<0.01）。总浓度和游离浓度的广泛差异表明需要仔细监测VPA浓度。其他药物的使用不仅会影响VPA的药代动力学，而且距上次给药的时间也会影响其浓度。非线性结合导致随着VPA总浓度升高，游离浓度大幅增加。我们在最低值和最高值时监测VPA的游离浓度和总浓度，并评估副作用和癫痫发作情况，以便更好地解读剂量需求。
