Estimation of the systemic bioavailability of timolol in man.

The systemic bioavailability of timolol, a beta-adrenergic receptor blocking agent, was calculated from published data in normal volunteers and uremic patients after oral doses. Equations based on the perfusion limited model that account for the biological determinants affecting drug disposition were derived and applied to calculate systemic bioavailability. The means of the fraction of the administered oral dose reaching the systemic circulations intact drug were calculated to be 0.58 and 0.60 for normal volunteers and uremic patients, respectively. Minimal first pass biotransformation during absorption was inferred from these figures for timolol when compared with other analogs such as propranolol and alprenolol, each of which undergoes an extensive first pass effect.