Plasma protein binding of penbutolol in pregnancy.
Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because shows linkage to alpha 1-glycoprotein, with no detectable binding to albumin. AAG levels change during pregnancy and so the binding of [3H]-penbutolol was compared in 11 pregnant patients and in 10 healthy women. Binding was obtained by ultrafiltration and measurement of the free fraction by scintillation spectrometry. The free penbutolol fraction was significantly higher in the pregnant women than in the controls (6.06 +/- 0.34 compared with 3.55 +/- 0.29, P less than 0.001). The AAG levels in the pregnant women were significantly lower (0.40 +/- 0.03 g/l) than in the controls (0.77 +/- 0.06 g/l) (P less than 0.001) which showed a significant correlation with the bound/free penbutolol ratio (r = 0.61, P less than 0.005). On the other hand there was no significant correlation with the extent of penbutolol's protein binding even though the albumin levels were lower in the pregnant women (2.83 +/- 0.17 compared with 4.86 +/- 0.17; P less than 0.001). Penbutolol's nK1a for AAG was lower in pregnant women, and this suggests that the fall in AAG levels is not the only factor involved in the reduced binding of penbutolol in pregnancy.
Aquirre
C
C
Department of Pharmacology, University of Basque Country, School of Medicine, Leioa (Vizcaya), Spain.
Rodriguez-Sasiain
J M
JM
Navajas
P
P
Calvo
R
R
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009961:Orosomucoid / Q000378:metabolism; D010394:Penbutolol / Q000097:blood*; D011247:Pregnancy / Q000378:metabolism*; D011412:Propanolamines / Q000097:blood*; D012709:Serum Albumin / Q000378:metabolism
D001798:Blood Proteins; D003278:Contraceptives, Oral, Hormonal; D009961:Orosomucoid; D011412:Propanolamines; D012709:Serum Albumin; D010394:Penbutolol