Infirmary, Manchester1 The oral pharmacokinetics of fluconazole were studied in three groups of volunteers (n = 5) with various degrees of renal function (GFR > 70 ml min-'; 20-70 ml min-; < 20 ml min-') and in a group of patients with chronic end-stage renal failure requiring regular haemodialysis. 2 The pharmacokinetics of fluconazole were markedly affected by impaired renal function with the elimination half-life in Group III (GFR < 20 ml min-) being approximately three times that observed in normal volunteers (Group I). 3 Fluconazole renal clearance was positively correlated with GFR. 4 Non-renal clearance of fluconazole decreased with decreasing renal function. 5 Approximately 38% of the 50 mg dose of fluconazole was removed by haemodialysis extending over a 3 h period.

The clinical, genetic, and pathologic findings, and the pertinent case histories in two families with idiopathic hemochromatosis are presented. These studies support the view that idiopathic hemochromatosis is a disease inherited in at least two ways. In one of these families, inheritance appeared to occur in an autosomal recessive manner, whereas in the other, autosomal dominant expression seemed evident. Evidence that an inability of the reticuloendothelial cells to handle iron may play a major role in the pathogenesis of hemochromatosis is presented. The early age of onset and poorer prognosis associated with the recessive inheritance suggest that the defect in reticuloendothelial cell function present in such cases is different from or more severe than those associated with dominant inheritance.