Design Considerations for Pharmacokinetic Studies During Pregnancy

Most of the interventions performed by obstetric providers involve the administration of drugs. Pregnant patients are pharmacologically and physiologically different from nonpregnant young adults. Therefore, dosages that are effective and safe for the general public may be inadequate or unsafe for the pregnant patient and her fetus. Establishing dosing regimens appropriate for pregnancy requires evidence generated from pharmacokinetic studies performed in pregnant people. However, performing these studies during pregnancy often requires special design considerations, evaluations of both maternal and fetal exposures, and recognition that pregnancy is a dynamic process that changes as gestational age advances. In this article, we address design challenges unique to pregnancy and discuss options for investigators, including timing of drug sampling during pregnancy, appropriate selection of control groups, pros and cons of dedicated and nested pharmacokinetic studies, single-dose and multiple-dose analyses, dose selection strategies, and the importance of integrating pharmacodynamic changes into these protocols. Examples of completed pharmacokinetic studies in pregnancy are provided for illustration.

Automated summary

Most interventions in obstetrics involve drug administration, but pregnant patients have different pharmacological and physiological characteristics compared to nonpregnant adults. Establishing appropriate drug dosing for pregnancy requires pharmacokinetic studies in pregnant individuals, which pose unique challenges due to the dynamic nature of pregnancy. This article discusses design considerations for such studies, including timing of drug sampling, control group selection, pros and cons of various study designs, dose selection strategies, and the importance of considering pharmacodynamic changes. Examples of completed pharmacokinetic studies in pregnancy are provided.