title: Detection of pivaloylcarnitine in pediatric patients with hypocarnitinemia after long-term administration of pivalate-containing antibiotics.
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.
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Sayaka
authors.initials: S
authors.lastname: Ichiki
authors.forename: Naruji
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Mihoko
authors.initials: M
authors.lastname: Mizuno
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Makino
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Kurono
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood* / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000009:adverse effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007223:Infant; D008297:Male; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C054040:pivaloylcarnitine; D002331:Carnitine