THE INFLUENCE OF GENDER AND SEX STEROID-HORMONES ON THE PLASMA-BINDING OF PROPRANOLOL ENANTIOMERS

1 Plasma binding of tritium-labelled racemic propranolol (P) was measu red by equilibrium dialysis. The unbound enantiomers were separated by h.p.l.c after chiral derivatization. The binding of (-)-P was higher than that of (+)-P. 2 Contrary to previous suggestions, a sex differen ce in the plasma binding of the P enantiomers (9 young women, 12 young men) was not observed. The unbound percentage of (-)-P was 9.2 +/- 1. 8 (mean +/- s.d.) in women vs 9.1 +/- 1.7 in men; for (+)-P it was 10. 8 +/- 1.8 vs 10.8 +/- 2.1. 3 In the nine women, the binding did not ch ange with fluctuating plasma oestradiol concentrations during the mens trual cycle. Testosterone cypionate doubled the circulating concentrat ions of testosterone in eight men but had no effect on P binding. 4 Et hinyl oestradiol (50 mug day-1) alone or together with norethindrone ( OCD) in eight of the women produced an increase in the unbound percent age of both (-)-P (11.4 +/- 2.6 vs 9.5 +/- 1.6 for control; P < 0.001) and (+)-P (13.2 +/- 2.5 vs 11.2 +/- 1.5 for control; P < 0.001). This was due to a decrease in the plasma concentrations of alpha1-acid gly coprotein from 0.54 +/- 0.11 mg ml-1 in control to 0.37 +/- 0.08 mg ml -1 (P < 0.001) during ethinyl oestradiol treatment. 5 Enantioselectivi ty in the unbound fraction of P increased with increasing total bindin g from a (-)/(+)-ratio of 0.93 at 84% binding to a (-)/(+)-ratio of 0. 78 at 94% binding (P < 0.001).