Pharmacokinetics and pharmacodynamics of atenolol during pregnancy and postpartum.
Preexisting hypertension complicates 5% of all pregnancies. The objective of this study was to evaluate steady-state atenolol pharmacokinetics and pharmacodynamics (n = 17) during the second trimester (2nd T), third trimester (3rd T), and 3 months postpartum. Pregnancy as compared to 3 months postpartum (nonpregnant control) resulted in significant (P < .05) changes, including the following: 42% (2nd T) and 50% (3rd T) increase in creatinine clearance, 38% (2nd T) and 36% (3rd T) increase in atenolol renal clearance, 12% (2nd T) and 11% (3rd T) decrease in atenolol half-life, 20% (2nd T) and 28% (3rd T) increase in cardiac output, 15% (2nd T) and 23% (3rd T) increase in resting heart rate, and 22% (2nd T) and 21% (3rd T) decrease in total peripheral resistance in subjects on steady-state oral atenolol for treatment of hypertension in pregnancy. In conclusion, the renal clearance of atenolol along with creatinine clearance is increased during pregnancy. However, this does not translate into an increase in apparent oral clearance of atenolol, possibly related to the high variability in bioavailability. Atenolol administration did not appear to change the pattern of the increase in cardiac output and the decrease in total peripheral resistance, which normally occurs during pregnancy.
Hebert
Mary F
MF
Department of Pharmacy, University of Washington, Seattle, WA 98195-7630, USA.
Carr
Darcy B
DB
Anderson
Gail D
GD
Blough
David
D
Green
Grace E
GE
Brateng
Debra A
DA
Kantor
Eric
E
Benedetti
Thomas J
TJ
Easterling
Thomas R
TR
D000328:Adult; D001262:Atenolol / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000097:blood / Q000188:drug therapy; D008895:Milk, Human / Q000187:drug effects / Q000378:metabolism; D049590:Postpartum Period / Q000097:blood* / Q000187:drug effects; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000097:blood* / Q000187:drug effects; D011263:Pregnancy Trimester, Third / Q000097:blood* / Q000187:drug effects
D001262:Atenolol; D003404:Creatinine