Relationship of carnitine and carnitine precursors lysine, epsilon-N-trimethyllysine, and gamma-butyrobetaine in drug-induced carnitine depletion.
Plasma concentrations and rates of urinary excretion of carnitine and some of its precursors were studied in three groups of children receiving drugs known to cause carnitine depletion. Patients in group A received pivampicillin and a molar equivalent of carnitine for 7 d. Patients in group B received pivampicillin with a 5.8-fold molar excess of carnitine for 1 wk. Patients in group C were treated chronically with valproic acid and received a molar equivalent (to valproic acid) of carnitine for 14 d. Patients in group A had markedly increased (16-fold) urinary carnitine ester excretion concomitant with diminished urinary free carnitine and gamma-butyrobetaine output and lower plasma free carnitine concentration. Supplementation with one molar equivalent of carnitine (to pivampicillin) was ineffective in preventing the reduction of plasma carnitine concentration observed with pivampicillin treatment alone. For group B patients, administration of excess carnitine resulted in a further increase (35-fold) of urinary carnitine ester output with no decrease of plasma carnitine concentration, urinary gamma-butyrobetaine, or free carnitine excretion. For patients in group C, the initially low plasma free and total carnitine concentrations and urinary output of carnitine and carnitine esters markedly increased with carnitine supplementation, but urinary excretion of gamma-butyrobetaine remained unchanged. The plasma concentrations and urinary output of L-lysine and epsilon-N-trimethyllysine remained unchanged within each group before and after treatment. A positive linear correlation was found between urinary epsilon-N-trimethyllysine and 3-methylhistidine output, indicating that the rate of epsilon-N-trimethyllysine excretion correlates with the amount of 3-methylhistidine liberated by protein turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
Melegh
B
B
Department of Pediatrics, University Medical School of Pécs, Hungary.
Pap
M
M
Bock
I
I
Rebouche
C J
CJ
D000293:Adolescent; D001437:Bacteriuria / Q000188:drug therapy; D001622:Betaine / Q000031:analogs & derivatives* / Q000652:urine; D002331:Carnitine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000652:urine*; D008297:Male; D010917:Pivampicillin / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000188:drug therapy; D014635:Valproic Acid / Q000494:pharmacology*
D010917:Pivampicillin; D001622:Betaine; C003712:trimethyllysine; C002889:gamma-butyrobetaine; D014635:Valproic Acid; D003404:Creatinine; D008239:Lysine; D002331:Carnitine