Pharmacokinetic and pharmacodynamic evaluation of atenolol during and after pregnancy.
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.


METHODS
Prospective study.


METHODS
Large university teaching hospital.


METHODS
Fourteen pregnant women who were receiving oral atenolol for cardiac disease were enrolled and 10 completed the study.


METHODS
Patients were studied for 12 hours during the third trimester (TT) and again 6 weeks postpartum (PP).


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.


CONCLUSIONS
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.
Hurst
A K
AK
School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Shotan
A
A
Hoffman
K
K
Johnson
J
J
Goodwin
T M
TM
Koda
R
R
Elkayam
U
U
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D000328:Adult; D019540:Area Under Curve; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001834:Body Water / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006331:Heart Diseases / Q000097:blood / Q000188:drug therapy / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006340:Heart Rate, Fetal / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption; D007743:Labor, Obstetric / Q000097:blood; D049590:Postpartum Period / Q000097:blood / Q000652:urine; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000097:blood / Q000188:drug therapy / Q000652:urine; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000652:urine; D011446:Prospective Studies; D012044:Regression Analysis; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D003404:Creatinine