将丙戊酸钠日服 2 次改为日服 1 次丙戊酸钠控释制剂的最佳策略是什么？：通过计算机模拟进行的检查和解答。

What Is the Best Strategy for Converting from Twice-Daily Divalproex to a Once-Daily Divalproex ER Regimen? : Examinations and Answers via Computer Simulations.

机构信息

Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois, USA.

出版信息

Clin Drug Investig. 2004;24(9):509-21. doi: 10.2165/00044011-200424090-00002.

DOI:10.2165/00044011-200424090-00002

PMID:17523713

Abstract

OBJECTIVE

To examine if, during conversion from conventional divalproex to once-daily divalproex extended-release (ER) tablets, plasma valproic acid (VPA) concentrations in the first 48 hours after conversion are maintained within the accepted therapeutic range (50-100 mg/L).

METHODS

Four distinct 12-hourly (q12h) divalproex to once-daily divalproex ER conversion strategies were explored: immediate, delayed, stepwise and mixed conversion. These strategies were each used in simulations for hypothetical adult patients being treated under different conditions: monotherapy (uninduced, at 1500 mg/day divalproex ER) and polytherapy on enzyme-inducing co-medications (induced, at 3000 and 4500 mg/day divalproex ER).

RESULTS

The proportion of uninduced patients expected to have minimum VPA concentrations (C(min)) >50 mg/L was 90% for immediate, 83% for stepwise and 82% for mixed-conversion strategies; only 52% undergoing a delayed-conversion strategy had C(min) >50 mg/L. More importantly, 33% of induced patients under-going delayed conversion to 3000 mg/day divalproex ER maintained an adequate VPA C(min). Maximum VPA concentrations (C(max)) attained after conversion to divalproex ER are unlikely to rise beyond the steady-state C(max) observed with divalproex q12h regimens with any conversion strategy tested in uninduced or induced patients. Marked perturbation in VPA concentration is not likely when converting to once-daily divalproex ER 'all-at-once' 12 hours after the last divalproex q12h dose. Stepwise and mixed-conversion strategies do not offer any advantage; delayed conversion may produce a large drop in VPA concentration.

CONCLUSIONS

An ideal conversion strategy for q12h divalproex to once-daily divalproex ER appears to be an immediate conversion 12 hours after the last divalproex q12h dose; it causes the least perturbation in plasma VPA, even for patients required to take high divalproex ER doses.

摘要

目的

考察在从传统丙戊酸钠转换为每日一次丙戊酸钠延长释放（ER）片剂期间，转换后 48 小时内的血浆丙戊酸（VPA）浓度是否保持在可接受的治疗范围内（50-100mg/L）。

方法

探索了四种不同的 12 小时（q12h）丙戊酸钠至每日一次丙戊酸钠 ER 转换策略：立即转换、延迟转换、逐步转换和混合转换。这些策略在模拟中分别用于不同条件下接受治疗的假设成年患者：单药治疗（未诱导，丙戊酸钠 ER 1500mg/天）和酶诱导共用药的多药治疗（诱导，丙戊酸钠 ER 3000mg/天和 4500mg/天）。

结果

预计未诱导患者的最小 VPA 浓度（C（min））>50mg/L 的比例为立即转换策略 90%，逐步转换策略 83%，混合转换策略 82%；只有 52%接受延迟转换策略的患者 C（min）>50mg/L。更重要的是，接受延迟转换至 3000mg/天丙戊酸钠 ER 的诱导患者中有 33%维持足够的 VPA C（min）。任何转换策略下，转换至丙戊酸钠 ER 后获得的最大 VPA 浓度（C（max））不太可能超过任何未诱导或诱导患者接受的丙戊酸钠 q12h 方案的稳态 C（max）。在最后一次丙戊酸钠 q12h 剂量后 12 小时，一次性转换至每日一次丙戊酸钠 ER 时，VPA 浓度不太可能出现明显波动。逐步和混合转换策略没有任何优势；延迟转换可能导致 VPA 浓度大幅下降。