Concentration-effect relationships of two infusion rates of the imidazoline antihypertensive agent rilmenidine for blood pressure and development of side-effects in healthy subjects

Aims The aim of this study was to compare the effect profiles of i.v. admin istered rilmenidine aimed at the same target plasma concentration, but atta ined with different rates. Methods The study was placebo-controlled, randomized, double-blind, double- dummy, three-way, cross-over in nine healthy volunteers. All subjects rando mly received either a fast infusion, a slow infusion or a placebo infusion. The target concentration was set at 8 ng ml(-1) with a fivefold difference in the time to reach the maximum concentration. Saccadic eye movements, el ectroencephalography (EEG), blood pressure and heart rate were measured eve ry half hour. Drug plasma concentrations, adverse events, salivary flow and visual analogue scales were obtained every hour. Results Changes in systolic/diastolic blood pressure at the end of the infu sion were (mean +/- s.d.) 13.3 +/- 16.4/7.9 +/- 7.5 mmHg with the fast infu sion and 16.3 +/- 12.7/10.2 +/- 7.9 mmHg during the slow infusion, compared with 0.0 +/- 13.2/1.3 +/- 8.3 mmHg for the placebo occasion. Decrease of s accadic peak velocity (SPV) at the end of the infusion was 18.0 +/- 5.2% du ring the fast infusion, 23.0 +/- 7.0% with the slow infusion, and 6.1 +/- 5 .2% with placebo. PK/PD analysis showed similar concentration-dependent lin ear reduction in SPV and blood pressure up to the maximum observed rilmenid ine plasma level for both the fast and the slow infusion. Conclusions The rate of infusion of rilmenidine in healthy volunteers does not influence the PK/PD relationship of saccadic eye movements and blood pr essure up to the maximum observed rilmenidine plasma concentrations. Rilmen idine causes clear concentration-dependent blood pressure reductions in hea lthy volunteers.