Was SB 209670 present in the circulation when CM nephropathy was determined?
CM-induced nephropathy is generally assessed from the 48-h (post-contrast) serum creatinine and may be defined as an impairment of renal function detected by an increase in serum creatinine of more than 44 µmol/l (or 25%), occurring within 3 days of contrast administration, in the absence of an alternative cause [1]. In the SB 209670 human CM nephropathy trial, the ET antagonist was given as a 100 µg/kg loading dose, initiated 30 150 min prior to contrast administration followed by a 12-h intravenous infusion (1 µg/kg/min). However, pharmacokinetic studies in healthy volunteers, using a similar dosage regimen show that when the intravenous infusion is stopped, blood levels of SB 209670 fall very rapidly, being virtually undetectable 24 h after the infusion was started [6]. To provide sustained blood levels, the ET antagonist should be an orally active agent administered 1 day before and for 2 7 days following contrast delivery. The importance of sustained drug cover in prevention studi
