Silvola Rebecca, O'Kane Aislinn, Heathman Michael, Marotta Hannah, Trussel Hayley, Ray Bobbie, Dowden Shelley, Masters Andrea R, Haas David M, Quinney Sara K
Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Metrum Research Group, Tariffville, Connecticut, USA.
CPT Pharmacometrics Syst Pharmacol. 2025 Mar;14(3):551-560. doi: 10.1002/psp4.13295. Epub 2025 Jan 31.
Enhanced Recovery After Surgery (ERAS) protocols for cesarean deliveries (CDs) utilize multimodal pain management strategies that often include gabapentin. While gabapentin is excreted in breast milk, its pharmacokinetics in immediately postpartum lactating women are not known. This observational pharmacokinetic study (NCT05099484) enrolled 21 healthy singleton pregnant individuals, ≥ 18 years old, undergoing CD and planning to breastfeed. Participants received 300 mg oral gabapentin before CD and every 6 h for 48 h per hospital protocol. Serial maternal plasma and breast milk samples were collected over a single dosing interval. Gabapentin pharmacokinetics were assessed using two structurally distinct population pharmacokinetic (POPPK) models to describe transfer of drug into breast milk utilizing (A) milk-to-plasma ratio and (B) inter-compartmental rate constants. These models were then used to estimate exposure to breastfed infants. Postpartum gabapentin plasma concentrations fit a 1-compartment model that was adapted to include breast milk concentrations. The two POPPK models both estimated relative infant doses (RID) of gabapentin < 0.15% of maternal dose within the first 48 h postpartum. Infant daily dose (IDD) from 24 to 48 h was estimated to be 0.0137 (0.0058-0.0316) mg/kg/day and 0.0139 (0.00041-0.0469) mg/kg/day by models A and B, respectively. These findings indicate limited neonatal exposure to gabapentin administered as part of a postpartum enhanced recovery after surgery protocol.
剖宫产（CD）的术后加速康复（ERAS）方案采用多模式疼痛管理策略，其中通常包括加巴喷丁。虽然加巴喷丁可通过母乳排泄，但其在产后即刻哺乳女性中的药代动力学尚不清楚。这项观察性药代动力学研究（NCT05099484）纳入了21名年龄≥18岁、接受剖宫产且计划进行母乳喂养的健康单胎孕妇。参与者在剖宫产术前按照医院方案接受300mg口服加巴喷丁，术后每6小时服用一次，共服用48小时。在单个给药间隔内收集产妇的系列血浆和母乳样本。使用两种结构不同的群体药代动力学（POPPK）模型评估加巴喷丁的药代动力学，以描述药物向母乳中的转运，模型（A）采用乳-血比，模型（B）采用隔室间速率常数。然后使用这些模型估计母乳喂养婴儿的暴露量。产后加巴喷丁血浆浓度符合单室模型，并进行了调整以纳入母乳浓度。两种POPPK模型均估计，产后48小时内加巴喷丁的相对婴儿剂量（RID）<产妇剂量的0.15%。模型A和模型B估计，产后24至48小时婴儿每日剂量（IDD）分别为0.0137（0.0058-0.0316）mg/kg/天和0.0139（0.00041-0.0469）mg/kg/天。这些发现表明，作为术后加速康复方案一部分给予的加巴喷丁对新生儿的暴露有限。
