Pharmacokinetic and Pharmacodynamic Evaluation of Atenolol during and after Pregnancy

Abstract

Study Objective. To evaluate changes due to pregnancy on atenolol's pharmacokinetics, response of maternal heart rate to atenolol, and the drug's effect on fetal heart rate.Design. Prospective study.Setting. Large university teaching hospital.Patients. Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study.Interventions. Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP).Measurements and Main Results. Fetal heart rates, and maternal heart rates at rest and during exercise were recorded. Maternal plasma and urine atenolol concentrations were measured. Average resting heart rates (TT 68 ± 10, PP 62 ± 9 beats/min) and maximum heart rate during exercise (TT 100 ± 6, PP 87 ± 7 beats/min) were significantly higher in the third trimester than postpartum (p<0.05). The 12‐hour atenolol area under the curve (TT 0.208 ± 0.061, PP 0.215 ± 0.089 ng/ml/day) and maximum plasma concentrations during the time of exercise tests (TT 1.07 ± 0.39, PP 1.14 ± 0.53 mmol/L) were not significantly different. Individual and population pharmacokinetics did not differ significantly between study periods. The fetal heart rate did not correlate with maternal atenolol concentration.Conclusion. Constant dosages of atenolol result in higher heart rates during pregnancy compared with the postpartum period. This lack of heart rate control is not due to significant changes in atenolol's pharmacokinetics or plasma concentrations.