PHARMACODYNAMICS AND PHARMACOKINETICS OF ORAL NITRENDIPINE SOLUTION IN HYPERTENSIVE PATIENTS WITH ADVANCED RENAL-FAILURE

Nitrendipine solution 5 mg . ml-1 in the dose of 5 mg was given orally to 20 patients with chronic renal failure and elevated diastolic bloo d pressure (greater-than-or-equal-to 110 mmHg), of whom 10 were on mai ntenance haemodialysis (endogenous creatinine clearance < 5 ml . min-1 ) and 10 were at the predialysis stage (endogenous creatinine clearanc e 5-20 ml . min-1). The aim of the study was to investigate the influe nce of kidney function and/or dialysis treatment on the pharmacokineti c and pharmacodynamic profile of a solution of nitrendipine and to ass ess its antihypertensive efficacy. After 10 min there was a significan t reduction in blood pressure from 188/113 to 173/100 (patients not de pendent on dialysis) and from 197/112 to 161/94 mmHg (patients depende nt on dialysis). The maximum fall in blood pressure (approximately 30% ) was attained after 90 min in the dialysis patients and after 120 min in the non-dialysis group. Blood pressure increased again about 3 h a fter the administration of nitrendipine but it was still below baselin e after 12 h. The terminal elimination half-life (4.1 h in the dialysi s patients and 3.6 h in non-dialysis patients) was similar to that obs erved in patients with normal renal function. The pharmacokinetics of nitrendipine did not differ between the dialysis and non-dialysis grou ps. There was a correlation between plasma concentration and the blood pressure reduction. The maximum plasma concentration of nitrendipine was reached after 0.5 h (median) and did not differ between the two gr oups. The mean maximum plasma concentration was 14.8 mug . l-1 in the study population as a whole, with comparable means in the dialysis (17 .3 mug . l-1) and non-dialysis (12.4 mug . l-1) groups. The nitrendipi ne solution proved to be effective in lowering acutely elevated blood pressure in patients with advanced renal failure and renal hypertensio n, and was well tolerated. The pharmacokinetics was not affected by re nal impairment or by dialysis.