Anderson Gail D, Carr Darcy B
Department of Pharmacy, University of Washington, Seattle, Washington, USA.
Clin Pharmacokinet. 2009;48(3):159-68. doi: 10.2165/00003088-200948030-00002.
In the US, approximately 12% of women have hypertension during their pregnancy. Antihypertensive drugs are often given to lower maternal blood pressure in those with severe hypertension to prevent stroke and hypertensive crises. There is no conclusive evidence that antihypertensive treatment is beneficial to the mother in mild to moderate hypertension; however, approximately 3% of all pregnant women receive an antihypertensive drug at some time during their pregnancy. There are only limited data on the effects of pregnancy on the pharmacokinetics of antihypertensive drugs. However, knowledge of the pharmacokinetic properties of a drug in the nonpregnant adult and use of a mechanistic-based approach allow an estimation of the effect of pregnancy on the pharmacokinetics of drugs when data are limited or not available. In general, an increased plasma volume and decreased protein binding can alter the volume of distribution of the drug. Clearance can increase or decrease, depending on the pathway of elimination of the drug. Through changes in the volume of distribution and clearance, pregnancy can cause a change in the elimination half-life, resulting in the need for modification of the dosing frequency. The few studies in pregnant women with hypertension have included small numbers of women in the third trimester and postpartum, with little or no data in early pregnancy. In addition, many studies evaluating the efficacy of antihypertensive medications have been performed using dosing regimens of medications that have not been substantiated by pharmacological data in pregnant women. There is a need for well designed pharmacokinetic and pharmacodynamic studies of antihypertensive medications that include analysis during all three trimesters of pregnancy and postpartum. Higher doses and altered dosage intervals may be needed for antihypertensive drugs used in pregnant women.
在美国，约12%的女性在孕期患有高血压。对于患有严重高血压的孕妇，常给予抗高血压药物以降低母体血压，预防中风和高血压危象。尚无确凿证据表明抗高血压治疗对轻度至中度高血压的母亲有益；然而，约3%的孕妇在孕期的某个时候会接受抗高血压药物治疗。关于妊娠对抗高血压药物药代动力学影响的数据有限。然而，了解非妊娠成年人中药物的药代动力学特性并采用基于机制的方法，在数据有限或无法获得时，可估计妊娠对药物药代动力学的影响。一般来说，血浆容量增加和蛋白结合减少可改变药物的分布容积。清除率可能增加或降低，这取决于药物的消除途径。通过分布容积和清除率的变化，妊娠可导致消除半衰期改变，从而需要调整给药频率。少数针对高血压孕妇的研究纳入的孕晚期和产后女性数量较少，孕早期的数据很少或没有。此外，许多评估抗高血压药物疗效的研究使用的给药方案并未得到孕妇药理学数据的证实。需要对抗高血压药物进行精心设计的药代动力学和药效学研究，包括孕期和产后三个阶段的分析。孕妇使用的抗高血压药物可能需要更高的剂量和改变给药间隔。
