Increased urinary losses of carnitine during ifosfamide chemotherapy

Chloroacetaldehyde and thiodiglycolic acid. two metabolites of ifosfamide, interfere with mitochondrial function and may sequester carnitine, Urinary excretion of carnitine was measured in five patients before and during a co ntinuous infusion of ifosfamide over 5 days at a dose of 2.8-3.2 g/m(2) per day. The excretion of free and total carnitine increased from 85 +/- 53 to 2697 +/- 1393 mu mol/day on the 1st day of chemotherapy and then gradually decreased, The average loss of carnitine during a chemotherapy cycle amoun ted to 8.5 mmol. The formation and excretion of esters of carnitine and met abolites of ifosfamide and/or a decreased renal tubular reabsorption could account for this marked loss, which might lead to symptomatic carnitine def iciency after several chemotherapy cycles.