PHARMACOKINETICS OF LINSIDOMINE (SIN 1) AFTER SINGLE AND MULTIPLE INTRAVENOUS SHORT INFUSIONS IN PATIENTS WITH RENAL-INSUFFICIENCY

Pharmacokinetic measurements were performed in two groups of patients with coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine (SIN 1). The drug was administered by intravenous sho rt time infusion in 12 CHD-patients with renal insufficiency (RI group , Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney fun ction (control group, Clcr: 88 +/- 22 ml/min). The measurement of plas ma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was fou nd to be suitable for an estimation of the SIN 1C related half-life of the terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated fr om plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total S IN 1C plasma profiles were equal after single and multiple administrat ion of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean m aximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0 .8 +/- 0.8% of dose) was significantly different from the correspondin g mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No d ifferences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any restrictions concerning repetitive SIN 1 dosage regi men should not be considered for CHD-patients with renal failure.