Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12947
Title: Influence of maternal plasma protein binding on fetal unbound plasma concentration of propranolol in the pregnant ewe.
Authors: Morgan, Denis J;Mihaly, G W;Czuba, M A;Ching, M S;Hardy, Kenneth John;Smallwood, R A
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Australia.
Issue Date: 1-Oct-1988
Citation: Journal of Pharmaceutical Sciences; 77(10): 835-7
Abstract: According to theory, for a drug of nonrestrictive, flow-limited clearance, a change during pregnancy of the unbound fraction (fu) of drug in maternal plasma should cause a change in steady-state unbound plasma drug concentration (Cu) in maternal plasma, which should also cause a change in fetal Cu. This theory was examined in 14 chronically cannulated, unanesthetized pregnant ewes in which 28 separate experiments were performed during the latter part of gestation. An initial bolus dose and 3-h constant rate infusion of propranolol were administered via the maternal jugular vein and steady-state maternal and fetal carotid arterial plasma total and unbound propranolol concentrations were measured. Fetal Cu (32 +/- 21 ng/mL) was significantly less than maternal Cu (78 +/- 52 ng/mL), due to previously demonstrated fetal hepatic extraction of propranolol. Notwithstanding fetal elimination, there was a significant correlation between fetal Cu and maternal Cu (r = 0.41, p less than 0.025). There was also a strong correlation between fetal Cu and the maternal unbound fraction of drug (fu; r = 0.75, p less than 0.001). We conclude that for propranolol, a drug of nonrestrictive, flow-limited clearance, changes in maternal fu can have a significant influence on fetal Cu, and therefore would be expected to influence the pharmacological effect of the drug in the fetus.
Internal ID Number: 3236224
URI: http://ahro.austin.org.au/austinjspui/handle/1/12947
URL: http://www.ncbi.nlm.nih.gov/pubmed/3236224
Type: Journal Article
Subjects: Animals
Blood Proteins.metabolism
Female
Fetal Blood.metabolism
Pregnancy
Pregnancy, Animal.blood
Propranolol.blood
Protein Binding
Sheep
Appears in Collections:Journal articles

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