Rizea-Savu Simona, Duna Simona Nicoleta, Panagiotopoulos Dimitrios, Sandulovici Roxana Colette
3S-Pharmacological Consultation & Research GmbH, Harpstedt, Germany.
Faculty of Pharmacy, Titu Maiorescu University, Bucharest, Romania.
Front Pharmacol. 2022 Apr 5;13:881198. doi: 10.3389/fphar.2022.881198. eCollection 2022.
Lisdexamfetamine is an inactive prodrug of dexamfetamine that is used for the second-line treatment of attention-deficit/hyperactivity disorder (ADHD) and moderate to severe binge eating disorder (BED). Once in the blood, the prodrug is hydrolyzed in erythrocyte cytosol, thus releasing the active dexamfetamine. We here present a fully validated HPLC-MS/MS analytical method for simultaneous determination of lisdexamfetamine and dexamfetamine in human plasma and the first published comparative bioavailability study of lisdexamfetamine including a GMP finished product formulated as oral solution. The Test (T)/Reference (R) ratios for the geometric means (%) of the primary pharmacokinetic (PK) parameters and their corresponding two-sided 90% confidence intervals (CIs) were contained within the predefined regulatory limits of 80.00-125.00% for both lisdexamfetamine and dexamfetamine. While for the lisdexamfetamine prodrug, PK results for the two formulations were slightly different due to the distinct dissolution state at administration, the PK parameters calculated for dexamfetamine were almost identical. A potential explanation of this phenomenon, already described in literature, is that biotransformation of lisdexamfetamine by red blood cells (rather than its release within the gastrointestinal tract) is the process controlling the rate of dexamfetamine delivery.
赖右苯丙胺是右旋苯丙胺的一种无活性前体药物，用于注意力缺陷多动障碍（ADHD）和中度至重度暴饮暴食症（BED）的二线治疗。一旦进入血液，该前体药物在红细胞胞质溶胶中被水解，从而释放出活性右旋苯丙胺。我们在此介绍一种经过充分验证的HPLC-MS/MS分析方法，用于同时测定人血浆中的赖右苯丙胺和右旋苯丙胺，以及首次发表的赖右苯丙胺比较生物利用度研究，该研究包括一种制成口服溶液的GMP成品。赖右苯丙胺和右旋苯丙胺的主要药代动力学（PK）参数几何均值（%）的试验（T）/参比（R）比值及其相应的双侧90%置信区间（CI）均在预先规定的80.00 - 125.00%的监管限度内。虽然对于赖右苯丙胺前体药物，由于给药时不同的溶解状态，两种制剂的PK结果略有不同，但计算得到的右旋苯丙胺的PK参数几乎相同。文献中已经描述了这种现象的一种可能解释，即赖右苯丙胺通过红细胞的生物转化（而非其在胃肠道内的释放）是控制右旋苯丙胺递送速率的过程。
