Pharmacokinetics during pregnancy: evidence-based maternal dose formulation

Objective: To review the literature regarding how drug pharmacokinetics differ between pregnant and nongravid women.Data Sources: Articles published between 1963 and 1997 were retrieved from the database of the National Library of Medicine for review, using the key words “pregnancy,” “pharmacokinetics,” and “human.” Additional articles and book chapters were identified from the bibliographies of articles retrieved.Methods of Study Selection: Articles had to include primary data that were not previously published. Data abstracted from articles meeting the inclusion criteria included: sample size, estimated gestational age, area under the curve, volume of distribution, maximum plasma concentration, steady-state concentration, half-life, time to maximum plasma concentration, clearance, and data from nonpregnant controls.Tabulation, Integration, and Results: Of more than 1000 articles published, 61 articles and book chapters reported relevant pharmacokinetic data, such as those listed, based on primary data. Only two studies synthesized pharmacokinetic data into guidelines for individualized clinical regimens.Conclusion: Available data regarding the pharmacokinetics of therapeutic regimens during pregnancy do not provide clinically relevant guidelines for the formulation of therapy for individual patients. Pharmacokinetic investigations during pregnancy that produce evidence-based guidelines for treating individual patients were identified as a major area of need. Minimum requirements are recommended for reporting pharmacokinetic studies in obstetrics.