JPET Introducing ALZET?ew Model 2006 Pump

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Czuba, M. A.
Right arrow Articles by Smallwood, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Czuba, M. A.
Right arrow Articles by Smallwood, R. A.

Effects of gestational age on the disposition of propranolol in pregnant sheep

MA Czuba, GW Mihaly, MS Ching, DJ Morgan, KJ Hardy and RA Smallwood

Department of Medicine, University of Melbourne, Austin Hospital, Australia.

Maternal and fetal disposition of the beta adrenoceptor blocking drug, propranolol was examined in the pregnant sheep from day 95 to day 140 (term, 145 days) of gestation. Propranolol was administered to the mother (bolus dose, 1.5 mg/kg followed by an infusion of 1.2 mg/kg/hr over 3 hr) to achieve an average steady-state maternal total drug concentration of 600 ng/ml. Total steady-state maternal plasma propranolol concentration was 666 +/- 266 ng/ml, reflecting a 4-fold variation in maternal drug clearance and a 14-fold variation in binding. Neither maternal clearance nor binding showed a significant change with gestational age. Total plasma drug concentrations in the fetus increased significantly with gestational age (r = 0.58, P less than .05), due to a concomitant increase in binding (r = 0.66, P less than .01). Fetal steady-state unbound drug concentrations were 50% of those seen in the mother, indicating that the fetus is capable of irreversible elimination of the drug. This ratio did not change with gestational age, suggesting that the capacity of the fetus to eliminate propranolol does not increase detectably in the latter part of pregnancy. The significant correlation between maternal and fetal unbound drug concentrations indicates that a major determinant of fetal exposure to propranolol is the clearance of the drug by the mother.

Volume 247, Issue 1, pp. 279-282, 10/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
S. C. S. Au-Yeung, D. W. Rurak, N. Gruber, and K. W. Riggs
A PHARMACOKINETIC STUDY OF DIPHENHYDRAMINE TRANSPORT ACROSS THE BLOOD-BRAIN BARRIER IN ADULT SHEEP: POTENTIAL INVOLVEMENT OF A CARRIER-MEDIATED MECHANISM
Drug Metab. Dispos., June 1, 2006; 34(6): 955 - 960.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. Kumar, G. R. Tonn, K. W. Riggs, and D. W. Rurak
Diphenhydramine Disposition in the Sheep Maternal-Placental-Fetal Unit: Gestational Age, Plasma Drug Protein Binding, and Umbilical Blood Flow Effects on Clearance
Drug Metab. Dispos., March 1, 2000; 28(3): 279 - 285.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.