Edwards Jeffrey E, Rudy Anita C, Wermeling Daniel P, Desai Nirmala, McNamara Patrick J
Graduate Center for Toxicology, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
Pharmacotherapy. 2003 Feb;23(2):153-8. doi: 10.1592/phco.23.2.153.32081.
To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model.
Single-dose, pharmacokinetic study.
University clinical research unit.
Eight lactating, nonsmoking, healthy women aged 24-32 years.
Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk.
Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk.
Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.
确定氢吗啡酮在母乳中的分布情况以及哺乳婴儿的潜在暴露量，以及被动扩散模型能否准确预测氢吗啡酮在乳汁中的分布。
单剂量药代动力学研究。
大学临床研究单位。
8名年龄在24 - 32岁之间的哺乳期、不吸烟的健康女性。
给这些女性鼻内给予2毫克盐酸氢吗啡酮，以表征其药代动力学及其向母乳中的转移程度。
使用液相色谱 - 串联质谱检测法分析血浆和乳汁样本。乳汁与血浆比值（M:P）计算为乳汁浓度 - 时间曲线下的总面积（AUC）除以血浆的总AUC。使用扩散模型计算体外预测的M:P比值。该模型纳入了乳汁和血浆中的蛋白质结合、向乳脂肪中的分配（全脂奶与脱脂奶比值）以及血浆与乳汁之间的pH分配。通过平衡透析法测定蛋白质结合情况。乳汁和血浆中的蛋白质结合均极少，未结合分数分别为1和0.84。全脂奶与脱脂奶比值为0.98，表明向乳脂肪中的分配极少。氢吗啡酮观察到的和预测的M:P比值±标准差分别为2.57±0.47和1.11±0.28。观察到的M:P比值的95%置信区间与预测的M:P比值的置信区间重叠，这一发现支持被动扩散和主动转运均为氢吗啡酮向乳汁转移的机制。
氢吗啡酮从血浆迅速分布到母乳中；然而，该药物不分配到脂肪中。哺乳婴儿将接受约0.67%的母亲剂量的氢吗啡酮（按体重调整）。由于这种暴露有限，需要进一步研究以确定对接受氢吗啡酮治疗的母亲所喂养的婴儿的任何潜在影响。
