The effect of pregnancy on drug pharmacokinetics

T he majority of pregnant women are healthy and many of them will be able to avoid taking drugs during their pregnancy. However, there exists a proportion of women who suffer from chronic illnesses, such as asthma, epilepsy and psychiatric disorders, or acute disorders such as infection and, therefore, may require either long-term or short-term medication. In such individuals, prescribers must choose the most appropriate drug and dosage regimen to ensure a good therapeutic outcome for the mother, while protecting the fetus from potential drug-induced teratogenicity, fetotoxicity or from short-term adverse effects in the neonatal period. To achieve a desired therapeutic effect, a drug, ultimately, must come into contact with the site of action, such as a specific receptor, enzyme or transport system. It is accepted currently that only the unbound portion (that portion which is not bound to carrier proteins) is accessibleto this site of activity and that, for most drugs, a predictable relationship exists between the concentration of unbound drug at this site and the concentration of total (bound and unbound) drug in the peripheral circulation. Thus, a knowledge of some drugs' plasma concentrations may be used as an indirect measure of drug action. When a drug is administered, a number of events must take place before the drug-active site interaction can occur to initiate and to maintain the pharmacological effect. First, absorption (unless the drug is deposited directly into the circulation) and distribution of the drug from the circulation into tissues are necessary. Termination of drug action is a function of clearance and may be considered as the efficiency of the body's elimination processes. The liver is the predominant site where lipophilic substances are rendered water soluble (metabolism), and then the kidney excretes these hydrophilic metabolites, or the parent drug if already it is sufficiently water soluble (excretion). During pregnancy, a number of physiological functions undergo substantial change with a return to the non-pregnant status during or soon after the puerperium. Some of these changes are of sufficient magnitude to influence drug absorption and disposition and, therefore, potentially to alter the concentration of drugs in the circulation and, for some drugs, their concentrations at the active sites. Thus, prescribers should be aware of these changes since a knowledge of these will define the principles which influence drug handling by pregnant women.