Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics

The Tohoku Journal of Experimental Medicine
Yoko NakajimaHajime Togari

Abstract

Some oral antibiotics contain a pivalate ester, because molecules with a pivalate entity show enhanced absorption in the intestine. Upon absorption, such a "prodrug" is broken down into the active form of a given antibiotic and a pivalate molecule, the latter of which is converted to pivaloylcarnitine through pivaloyl-CoA and is excreted in the urine. Long-term administration of drugs containing pivalate decreases blood carnitine level and causes defects in fatty acid oxidation. Here, we used liquid chromatography tandem mass spectrometry to measure carnitine and pivaloylcarnitine levels in two patients (Patient 1: 16-month-old boy and Patient 2: 18-month-old boy) with secondary carnitine deficiency and hypoglycemic convulsions caused by pivalate-containing antibiotics. Both patients were administered excessive doses of pivalate for the long-term treatment of recurrent infection, and consequently, the serum free carnitine levels were very low (Patient 1: 1.0 micromol/L and Patient 2: 0.4 micromol/L), compared to normal range of 33.3-43.0 micromol/l, while the serum pivaloylcarnitine levels were elevated from normally undetectable level (Patient 1: 3.7 micromol/L and Patient 2: 1.6 micromol/L). Patient 1 recovered immediately af...Continue Reading

References

Sep 1, 1992·Scandinavian Journal of Clinical and Laboratory Investigation·E HolmeI Nordin
Jan 1, 1995·The Tohoku Journal of Experimental Medicine·T ItoH Togari
Nov 14, 2002·Pharmacological Reviews·Eric P Brass
Apr 24, 2003·Clinical Pharmacology and Therapeutics·Eric P BrassCharles L Hoppel

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Citations

Apr 10, 2016·The Journal of Pediatrics·Hironori KobayashiSeiji Yamaguchi
Dec 3, 2013·Molecular Genetics and Metabolism·François BoemerFrançois-Guillaume Debray
Mar 19, 2013·Clinica Chimica Acta; International Journal of Clinical Chemistry·Nils JanzenJohannes Sander
Jun 4, 2014·Medicina clínica·Raquel YahyaouiFrançois Boemer
Mar 1, 2020·BMC Health Services Research·Shinya TsuzukiNorio Ohmagari
Jul 22, 2021·International Journal of Neonatal Screening·Yosuke ShigematsuGo Tajima

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