Safety and carnitine status after oral administration of S-1108 to pediatric patients

Abstract

To investigate the clinical safety of S-1108, which contains pivalic acid, we measured both free carnitine, total carnitine and pivaloylcarnitine in plasma and urine, and the acyl/free carnitine ratio in the plasma of pediatric patients (4-17 yrs) with pneumonia, bronchitis, and tonsillitis. The results are as follows:
1. Mean free and Total carnitine concentrations in the plasma of pediatric patients (n=120; male, 63; female, 57) untreated with S-1108 were 42.8±9.5 and 54.5±11.8 nmol/ml, respectively.
2. After the 4 to 12 days of treatment with daily dose of 6-18 mg/kg/day, free carnitine concentrations were reduced in all cases. The degree of free carnitine reduction depended on the dose and duration of S-1108 treatment. Free carnitine levels, however, showed a tendency to increase after the cessation of administration, and returned to normal within 3-4 days to about 7 days, at the lower and higher doses, respectively. Free carnitine concentrations in plasma were moderately reduced by 20% of pretreatment values at the highest doses, 16-18 mg/kg/day, however, there seemed to be full reversibility of carnitine status within a few days after cessation of treatment.
3. The acyl/free carnitine ratio, a parameter of secondary carnitine deficiency, was less than 0.5 in almost all cases during treatment, and there was no change in the ratio before, during and after S-1108 treatment.
4. No symptoms or adverse effects associated with carnitine deficiency were observed in any of the patients.
Regarding carnitine status, S-1108 was demonstrated to be safe and well tolerated when administered at the recommended dosage schedule.