Perturbation of paracetamol urinary metabolic ratios by urine flow rate

The effects of high and low urine flow rates on the urinary metabolic ratios for paracetamol glucuronidation, sulphation and oxidation were determined at steady-state in seven healthy young adult volunteers. Metabolic partial clearances were unaffected by urine flow rate, but individual paracetamol metabolic ratios varied 2.5- to 3.2-fold over a 7.4-fold range of urine flow rates (0.81-6.00 ml min-1). The change in metabolic ratios was due entirely to a 2.5-fold change in renal clearance of unchanged paracetamol. These data emphasise the limitations of the metabolic ratio as a measure of intrinsic clearance for compounds which undergo some degree of tubular reabsorption.