Plasma protein binding of ethinyloestradiol: effect of disease and interaction with drugs
Pacifici, G.M.; Viani, A.; Rizzo, G.; Carrai, M.
International Journal of Clinical Pharmacology Therapy and Toxicology 27(7): 362-365
1989
ISSN/ISBN: 0174-4879 PMID: 2777426 Document Number: 336524
The protein binding of ethinyloestradiol (EE2) was investigated in the plasma from 14 healthy volunteers, 10 patients with hyperbilirubinemia, 10 patients with liver cirrhosis and 10 patients with renal failure. Binding assay was performed by equilibrium dialysis at 37.degree. C. The unbound fraction (mean .+-. SD) of EE2 was 1.17 .+-. 0.12 (volunteers), 2.74 .+-. 0.77 (hyperbilirubinemics; p < 0.001) 1.51 .+-. 0.31 (cirrhotics; p < 0.01) and 1.44 .+-. 0.11 (renal failure; p < 0.001). Studies with isolated albumin and alpha-1-acid glycoprotein showed that albumin is the major plasma protein to bind EE2. Warfarin (75 .mu.M) and diazepam (75 .mu.M) increased by 5.0% and 3.0%, respectively, the unbound fraction of EE2 when albumin concentration was 15 .mu.M. Under similar conditions, digitoxin did not modify the binding of EE2. At therapeutic concentrations, warfarin and diazepam did not affect the binding of EE2 in plasma.