Pelzl G, Mamoli B
II. Neurologische Abteilung des Neurologischen Krankenhauses Rosenhügel, Wien.
Wien Klin Wochenschr. 1992;104(10):286-9.
A prospective clinical pharmacokinetic study was carried out in 10 adult patients with primary or secondary generalized tonic-clonic seizures on the efficacy of valproic acid (VPA) administered as a single daily dose in comparison with divided doses thrice daily. The observation period covered 28 weeks. Without changing the total daily dosage the once-daily treatment proved to be of at least equal clinical efficacy. The single daily dose was well tolerated without any increase in adverse effects. Following a once-daily evening dose the VPA plasma profiled displayed--as expected--a steep increase during the early evening hours, reaching a maximal value around 2 a.m.; afterwards the plasma levels decrease continuously until the next evening. By comparison, the thrice-daily regimen gave maximal VPA levels at 2 p.m. With respect to the pharmacokinetic parameters, the minimum VPA plasma concentrations proved to be significantly lower, and the fluctuations significantly higher during the once-daily administration period the mean maximum VPA plasma level was higher, but not significantly so. The bioavailability was not affected by the change in dosage regimen. Since once-daily evening administration results in better patient compliance it seems appropriate to initiate VPA therapy with this simplified dosage regimen. For patients with inadequate seizure control on multiple daily doses of VPA it seems feasible--from a theoretical point of view--that the rate of attacks might be reduced after a changeover to a once-daily evening dosage regimen, but this has not yet been proven in clinical practice.
对10例原发性或继发性全身强直阵挛性发作的成年患者进行了一项前瞻性临床药代动力学研究，比较了丙戊酸（VPA）每日单次给药与每日三次分剂量给药的疗效。观察期为28周。在不改变每日总剂量的情况下，每日一次治疗被证明具有至少同等的临床疗效。每日单次剂量耐受性良好，不良反应未增加。在每日一次晚间给药后，VPA血浆曲线显示——正如预期的那样——在傍晚早期急剧上升，在凌晨2点左右达到最大值；此后血浆水平持续下降直至次日傍晚。相比之下，每日三次给药方案在下午2点达到VPA最高水平。关于药代动力学参数，在每日一次给药期间，VPA血浆最低浓度显著较低，波动显著较高，VPA血浆平均最高水平较高，但差异不显著。生物利用度不受给药方案变化的影响。由于每日一次晚间给药可提高患者依从性，因此采用这种简化给药方案启动VPA治疗似乎是合适的。对于每日多次服用VPA但癫痫控制不佳的患者，从理论角度来看，转换为每日一次晚间给药方案后发作率可能会降低，但这尚未在临床实践中得到证实。
