81 A NOVEL FORM OF DRUG-INDUCED OAEKITIHE INSUFFICIENCY

Pivalic acid is widely used in pharmacology to facilitate drag absorption. As a fatty acid it may react with carnitine /C/ but further degradation via beta oxidation is impossible due to its structure. It is possible therefore, that pivalate containing drugs can cause C insufficiency. Urinary excretion of C /0 to 7 days daily/ and fasting plasma levels of C, beta hydroxybutyrate /BHB/, FFA, triglyoerides /TG/ and glucose /BG/, /day 0 and 7/ were aeasured in 7 children during pivampicillin treatment /2g/day/. Drug administration was followed by a prompt and sustained increase in total C excretion /0.27-0.07 YS 1.24±0.18 mmol/day, day 0 vs 1, aeans±SEM, p< 0.05/ which was mainly due to a rise in aoyl C excretion, the excretion of free C declined. The plasma level of total C /42.7±5.4 vs 26.2±2.1 umol/1, p<0.05/, BHB /0.27±0.13 vs 0.04±0.02 maol/l, p<0.05/ and urea /4.61±0.25 vs 3.74±0.2 nmol/l, p<0.02/ decreased and acyl C increased /11.6-1.9 vs 17.7±1.7 umol/l, p<0.05/ with no change in TG, FFA and BG levels. Conclusions: 1., Decreased availability of free C may cause carnitine insufficiency /increase of the acyl:free C ratio/ aad as a consequence ketogenesis and urea synthesis may be impaired; 2., Increased excretion of acyl C, on the other hand, may represent a novel xenobiotio function.