INFLUENCE OF MULTIPLE-DOSE ADMINISTRATION OF CEFETAMET PIVOXIL ON BLOOD AND URINARY CONCENTRATIONS OF CARNITINE AND EFFECTS OF SIMULTANEOUS ADMINISTRATION OF CARNITINE WITH CEFETAMET PIVOXIL

Abstract

Cefetamet pivoxil (CEMT-PI), a drug of pivaloyloxymethyl group, was investigated for its impact on the carnitine blood homeostasis and renal excretion upon administering CEMT-PI alone, and CEMT-PI simultaneously with carnitine. 500 mg of CEMT-PI (group A) and 500 mg of CEMT-PI and an equimolar amount (200 mg of carnitine) of levocarnitine chloride (group B) were administered twice a day for 7 and 1/2 consecutive days to 5 healthy volunteers (group A) and 3 healthy volunteers (group B). No serious side effects nor abnormal values in physical and laboratory tests were observed throughout the study in both groups. During the treatment period, plasma total carnitine decreased slowly down to 25.5 microM (group A) and 38.8 microM (group B) and plasma free carnitine reached steady state levels at 17.7 microM (group A) and 29.2 microM (group B) on day 5. These concentrations represent 45 and 37% in group A, 66 and 58% in group B of the average pre-treatment baseline levels. Plasma pivaloylcarnitine quickly reached plateau levels of 6.12 microM (group A) and 4.05 microM (group B) on day 4. After treatment stop, plasma total and free carnitine returned to the pretreatment baseline level within 5 days (group A) and 3 days (group B), and plasma pivaloylcarnitine was detectable until day 7 of the treatment-free follow up in both groups. Although carnitine was given concurrently at a dose equimolar to the ingested amount of pivalic acid in group B, the plasma total and free carnitine exhibited a decrease. This was considered attributable to the fact that the bioavailability of carnitine is as low as 16% when administered orally, which is considerably less compared to the 55% bioavailability of cefetamet pivoxil.