Indenolol kinetics versus pharmacodynamics in hypertension.

A kinetic model has been employed to compare the duration of the antihypertensive activity of indenolol to its plasma half-life both after single administration and at steady-state. After a 14 day run-in period with placebo, 60 or 120 mg indenolol were given to hypertensive patients I or II grade, according to W.H.O. guidelines, once a day for 14 days. Blood samples were drawn and blood pressure recorded at intervals after the first dose, during treatment and after the last dose of the compound. Both plasma concentration and mean arterial pressure difference curves were fitted by a first order input-output model, where plasma half-life was 4 h, while pharmacological half-life was 24 h for both dose-levels tested. Therefore, with once-a-day dose regimen an accumulation of the antihypertensive effect of indenolol was demonstrated, with 99% steady-state of blood pressure reached after 7 days, while the drug did not accumulate in the central compartment.