Modelling the pharmacokinetics and pharmacodynamics of trimazosin

The pharmacokinetics and pharmacodynamics of trimazosin are described following both intravenous and oral administration to 6 normotensive, male volunteers. The IV and oral drug and metabolite (1-hydroxytrimazosin) concentration data are fitted simultaneously to the same pharmacokinetic model. The pharmacodynamic response, change in systolic blood pressure following 5 min in the erect posture, is described using several possible models. The most efficient is one which attributes the response to both the parent drug and its principal metabolite. The response following oral administration is also consistent with this model. It appears that the reduction in blood pressure following administration of trimazosin at steady state may be governed by the concentration of metabolite.