Pivampicillin-promoted excretion of pivaloylcarnitine in humans

Abstract

Pivampicillin treatment of seven children (five boys and two girls) for 7 days significantly reduced the amounts of total acid-soluble carnitine, free carnitine, and long-chain acylcarnitines and increased the amounts of acid-soluble acylcarnitine in plasma. The fasting plasma levels of 3-hydroxybutyrate at the end of treatment were 15% of the control value. The levels of free fatty acids were decreased, whereas triglyceride levels were unaffected, indicating impaired fat metabolism. Daily urinary excretion of total carnitine was four to five times higher than controls after the first day of treatment, although the amounts of free carnitine and acetylcarnitine were decreased. The urinary acylcarnitines were isolated and characterized by gas chromatography/electron impact mass spectrometry and fast-atom bombardment mass spectrometry. Pivaloylcarnitine was the predominant urinary acylcarnitine; it represented greater than 96% of the increased excretion of total carnitine and 75-80% of the total conjugated pivalic acid. The renal clearance of acylcarnitines was comparable to that of creatinine, indicating no reabsorption of pivaloylcarnitine. These data suggest a detoxification function of carnitine for pivalic acid in humans.