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The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Background. This multicentre, open-label prospective, randomized, comparative-group study evaluated the effects of maintaining haemoglobin (Hb) in pre-dialysis chronic kidney disease (CKD) patients. Methods. A total of 197 patients were randomized to start subcutaneous epoetin-a (SC-EPO; EPREX Õ ; 1000 U twice weekly) at an early stage of anaemia to maintain Hb at 11.0 AE 1.0 g/dl (group A, n ¼ 65), or to allow Hb to fall to 9.0 g/dl before starting SC-EPO (group B, n ¼ 132) (2000 U three times weekly); and subsequently maintaining Hb at 11.0 AE 1.0 g/dl.Results. Of 132 patients randomized to group B, 55 progressed to treatment (-trigger). The study was prematurely terminated due to contraindication of the subcutaneous administration route. Mean weekly EPO doses at 1 year were 1471 U for group A; 820 U for group B; final doses were 2281 U for group A; 2099 U for group B. There was no significant difference between groups A and B with regard to left ventricular mass (À12.5 vs À9.7%; P ¼ 0.82). In groups A and B, 48% and 52%, respectively, terminated the study because of dialysis/death, after a median of 36.3 and 27.3 months, respectively. Conclusion. Early intervention to correct anaemia in CKD patients did not have a significant impact on LVM, the primary efficacy variable. Time to dialysis/death was not significantly different between groups A and B.