Influence of renal dysfunction on the pharmacokinetics of the selective Na+/H+ exchange inhibitor EMD 87 in patients with chronic heart failure

Background: Chronic heart failure (CHF) is a potential indication for the administration of EMD 87 580, a selective Na+/H+ exchange inhibitor. CHF is often accompanied by renal dysfunction, which is known to affect the pharmacokinetics of compounds predominately cleared by the kidneys. We examined the influence of renal dysfunction on the pharmacokinetics of EMD 87 580 in patients with CHF. Methods: 21 patients with CHF and normal renal function (Group 1) and 9 patients with CHF and renal dysfunction (Group 2) received EMD 87 580 orally over 8 days. The mean creatinine clearance (CrCl) in Group 1 was 99.7 ml/min. 12 patients in this group were randomized to receive two doses of EMD 8 7580 (7 patients 2 x 5 0 mg and 5 patients 2 x 100 mg). The 9 patients in Group 2 with renal dysfunction (mean CrCl = 49.5 ml/min) received 50 mg EMD 87580 once daily. Plasma and urine samples were collected for pharmacokinetic assessment. Results: In CHF patients with renal dysfunction EMD 87580 clearance was reduced to approximately 50% compared to Group 1, i.e. 6.80 ml/min (4.89 - 11.60) vs. 12.73 ml/min (8.93 - 22.2 1), p