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

Yoko Nakajima, Tetsuya Ito, Yasuhiro Maeda, Sayaka Ichiki, Naruji Sugiyama, Mihoko Mizuno, Yasuko Makino, Tokio Sugiura, Yukihisa Kurono, Hajime Togari

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 after the glucose infusion, whereas Patient 2 remained symptomatic even after blood glucose level was normalized and fully recovered after carnitine supplementation. The urine pivaloylcarnitine level in Patient 2 was increased during carnitine supplementation (from 821.4 to 12,200 micromol/g creatinine) even after discontinuing the antibiotics, indicating that a considerable amount of pivalate was accumulated in the tissues. In conclusion, long-term administration of pivalate-containing antibiotics should be avoided particularly in children.

Original languageEnglish
Pages (from-to)309-313
Number of pages5
JournalThe Tohoku Journal of Experimental Medicine
Volume221
Issue number4
DOIs
Publication statusPublished - 27-10-2010

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Pediatrics
Carnitine
Anti-Bacterial Agents
Molecules
Liquid chromatography
Prodrugs
Coenzyme A
Hypoglycemic Agents
Mass spectrometry
Blood Glucose
pivaloylcarnitine
Creatinine
Esters
Blood
Fatty Acids
Urine
Tissue
Glucose
Oxidation
Defects

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nakajima, Yoko ; Ito, Tetsuya ; Maeda, Yasuhiro ; Ichiki, Sayaka ; Sugiyama, Naruji ; Mizuno, Mihoko ; Makino, Yasuko ; Sugiura, Tokio ; Kurono, Yukihisa ; Togari, Hajime. / Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics. In: The Tohoku Journal of Experimental Medicine. 2010 ; Vol. 221, No. 4. pp. 309-313.
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Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics. / Nakajima, Yoko; Ito, Tetsuya; Maeda, Yasuhiro; Ichiki, Sayaka; Sugiyama, Naruji; Mizuno, Mihoko; Makino, Yasuko; Sugiura, Tokio; Kurono, Yukihisa; Togari, Hajime.

In: The Tohoku Journal of Experimental Medicine, Vol. 221, No. 4, 27.10.2010, p. 309-313.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics.

AU - Nakajima, Yoko

AU - Ito, Tetsuya

AU - Maeda, Yasuhiro

AU - Ichiki, Sayaka

AU - Sugiyama, Naruji

AU - Mizuno, Mihoko

AU - Makino, Yasuko

AU - Sugiura, Tokio

AU - Kurono, Yukihisa

AU - Togari, Hajime

PY - 2010/10/27

Y1 - 2010/10/27

N2 - 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 after the glucose infusion, whereas Patient 2 remained symptomatic even after blood glucose level was normalized and fully recovered after carnitine supplementation. The urine pivaloylcarnitine level in Patient 2 was increased during carnitine supplementation (from 821.4 to 12,200 micromol/g creatinine) even after discontinuing the antibiotics, indicating that a considerable amount of pivalate was accumulated in the tissues. In conclusion, long-term administration of pivalate-containing antibiotics should be avoided particularly in children.

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