Effect of Pregnancy on the Pharmacokinetics of Antihypertensive Drugs

Abstract

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.