Impaired ketogenesis in carnitine depletion caused by short-term administration of pivalic acid prodrug.

• Long-term treatment with pivalic acid prodrug results in impaired ketone-body production. Therefore, it was of interest to investigate whether short-term treatment had any influence on the fatty acid oxidation. In this study six healthy males were given 1200 mg per day of pivmecillinam for 12 days to induce carnitine deficiency. The concentration of free carnitine in serum was reduced from a mean of 42.8 mumol/liter (range, 31-48) to 11.6 mumol/liter (range, 7.0-24), but the muscle carnitine concentration was not reduced. A 36-h fasting test was performed before and after drug administration to study the effect on ketone-body production. After treatment, the two subjects with the lowest level of serum free carnitine at the end of the fasting period had impaired ketogenesis. This indicates a carnitine deficiency in the liver which was reflected in the free carnitine concentration for by mobilization of muscle carnitine. We conclude that there is a substantial risk to develop carnitine deficiency and impaired fatty acid oxidation in the liver during short-term treatment with drugs conjugated with pivalic acid.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Keyword

Adult

Amdinocillin Pivoxil

pharmacology

Carnitine

blood

deficiency

metabolism

Fatty Acids

metabolism

Fatty Acids

Nonesterified

blood

Humans

Ketone Bodies

biosynthesis

Liver

metabolism

Male

Muscle

Skeletal

drug effects

metabolism

Oxidation-Reduction

Pentanoic Acids

pharmacology

Prodrugs

pharmacology

Publication and Content Type

ref (subject category)

art (subject category)