口服拉贝洛尔母乳药动学的风险评估与哺乳期合理用药

Risk assessment of the human milk pharmacokinetics and rational drug use during lactation by taking labetalol orally

目的:基于口服拉贝洛尔在妊娠期高血压产妇的乳汁药动学,评估哺乳期用药风险和干预哺乳时间,促进哺乳期合理用药。方法:选取2016年10月-2017年7月住院分娩的60例妊娠期高血压产妇泌乳后口服拉贝洛尔片的乳汁,采用超高效液相色谱串联质谱法(UPLC-MS/MS)测定乳汁药物浓度,并计算药动学相关参数和用药风险评估指标。结果:妊娠高血压产妇产后继续服用拉贝洛尔(100 mg,q8h,n=60),乳汁中药动学参数:达峰时间(tmax)为(2.7±0.9)h、达峰浓度(Cmax)为(268.0±71.9)ng·mL-1、半衰期(t1/2)为(4.1±1.7)h。母乳用药风险评估指标,TID(theoretical infant dose,理论婴儿剂量)为(0.026±0.012)(95%CI:0.025~0.027)mg·kg-1·d-1,RID(relative infant dose,相对婴儿剂量)为(0.53%±0.13%)(95%CI:0.49%~0.58%)。结论:妊娠期高血压产妇产后继续服用拉贝洛尔,受哺婴儿理论剂量和相对剂量均低于风险限,安全性较高,可在服药3~4 h后到下次服药周期前按需哺乳。

OBJECTIVE To assess the drug risk and intervene breastfeeding time,promote rational drug use and breastfeeding based on the human milk pharmacokinetics of gestational hypertension patients taking labetalol.METHODS From October2016 to July 2017,60 human milk samples were taken from gestational hypertension patients who took labetalol as soon as lactating.Then the human milk drug concentrations were tested by ultra-high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）,and the pharmacokinetics parameters and the drug risk assessment indexes were calculated.RESULTS The gestational hypertension patients continued taking labetalol after delivery（100 mg q8 h,n=60）,the human milk pharmacokinetic parameters were：tmax（2.7±0.9）h,Cmax（268.0±71.9）ng·mL^-1,t1/2（4.1±1.7）h.The drug risk assessment indexes were：TID（theoretical infant dose）（0.026±0.012）（95% CI：0.025-0.027）mg·kg^-1·d^-1,RID（relative infant dose）（0.53%±0.13%）（95% CI：0.49%-0.58%）.CONCLUSION The gestational hypertension patients continue taking labetalol after delivery,TID and RID are both well below the drug risk limit,showing good drug safety.Besides,reasonable breastfeeding education advises that mothers should breastfeed according to the actual needs and feed 3–4 hours after medication till the next cycle.