Pharmacokinetics and safety of antimicrobial agents during pregnancy.

The use of antimicrobial agents during pregnancy poses unique concerns because of both potential toxicity and special pharmacokinetic considerations that have important therapeutic implications for both mother and fetus. Various physiologic adaptations occur with advancing gestation, including marked increases in maternal intravascular volume, glomerular filtration, and hepatic and metabolic activities; thinning and maturation of the fetomaternal membrane; and increases in transplacental diffusion capacity. The net result is that maternal antimicrobial concentrations tend to be 10%-50% lower in late pregnancy and the immediate postpartum period than in the nonpregnant state. Placental transfer of antimicrobial agents and their excretion in amniotic fluid or breast milk are similarly affected by hemodynamic changes, membrane transport characteristics, and maturation or metabolic activity of the specific organs involved. Review of the literature suggests that, although the need for caution in the use of antimicrobial agents during pregnancy has been well emphasized, firm data on the pharmacokinetics, efficacy, and optimal use of these drugs in this situation are extremely sparse and urgently needed. However, recommendations regarding the use of specific antibacterial, antifungal, antiviral, and antiparasitic agents against selected infections during pregnancy can be made.