Pregnancy and the postpartum period are associated with several physiological changes that can alter the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. For certain drugs, dosing changes may be required during pregnancy and postpartum to achieve drug exposures comparable to what is observed in non-pregnant subjects. There is very limited data on fetal exposure of drugs during pregnancy, and neonatal exposure through transfer of drugs via human milk during breastfeeding. Very few systematic clinical pharmacology studies have been conducted in pregnant and postpartum women due to ethical issues, concern for the fetus safety as well as potential legal ramifications. Over the past several years, there has been an increase in the application of modeling and simulation approaches such as population PK (PopPK) and physiologically based PK (PBPK) modeling to provide guidance on drug dosing in those special patient populations. Population PK models rely on measured PK data, whereas physiologically based PK models incorporate physiological, preclinical, and clinical data into the model to predict drug exposure during pregnancy. These modeling strategies offer a promising approach to identify the drugs with PK changes during pregnancy to guide dose optimization in pregnancy, when there is lack of clinical data. PBPK modeling is also utilized to predict the fetal exposure of drugs and drug transfer via human milk following maternal exposure. This review focuses on the current status of the application of PBPK modeling to predict maternal and fetal exposure of drugs and thereby guide drug therapy during pregnancy.

Background:Microsampling is a technique that utilizes a very small volume of biological matrix, typically less than 50 µL, for quantitatively analyzing chemicals, drugs, and biologics. The use of filter paper for blotting blood samples, usually referred to “Dried Blood Spots”, is an example of a microsampling approach, which has been established since the early 1960s. However, non-homogeneous sample spread, the influence of hematocrit, improper volume measurement, and environmental degradation are major bottlenecks to the widespread adoption of this technique in routine clinical sample analysis. Novel methods have overcome several of these issues; however, assays using these microsampling tools involve variable steps/approaches.Methods:A novel microsampling device called Volumetric Absorptive microsampling (VAMS), developed in 2014, appears to have resolved the sample inhomogeneity inherent to dried blood spots, with improved precision in the volume of sample collected for measuring drug concentration. A literature search was conducted to identify several analytical and pharmacokinetic studies that have used VAMS in recent years.Results:The key factors for proper experimental design and optimization of the extraction of drugs and metabolites of interest from the device were summarized. This review focuses on VAMS and elaborates on bioanalytical factors, method validation steps, and scope of this technique in clinical practice.Conclusions:The promising microsampling method VAMS is especially suited for conducting pharmacokinetic studies with very small volumes of blood, especially in special patient populations. Clinical validation of every VAMS assay must be conducted prior to the routine practical implementation of this method.