title: Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous short infusions in patients with renal insufficiency.
abstract: 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 short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was found 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 from plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles were equal after single and multiple administration of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean maximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No differences 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 regimen should not be considered for CHD-patients with renal failure.
authors.affiliation: Academisch Ziekenhuis V.U.B., Nefrologie, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Sennesael
authors.forename: D
authors.initials: D
authors.lastname: Verbeelen
authors.forename: S
authors.initials: S
authors.lastname: Degré
authors.forename: P
authors.initials: P
authors.lastname: Unger
authors.forename: J C
authors.initials: JC
authors.lastname: Stolear
authors.forename: J
authors.initials: J
authors.lastname: Ostrowski
authors.forename: H M
authors.initials: HM
authors.lastname: von Hattingberg
authors.forename: W
authors.initials: W
authors.lastname: Gaertner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D014665:Vasodilator Agents; C002385:linsidomine; D008981:Molsidomine