MULTIPLE-DOSE PHARMACOKINETICS AND BIOEQUIVALENCE OF L-CARNITINE 330-MG TABLET VERSUS 1-G CHEWABLE TABLET VERSUS ENTERAL SOLUTION IN HEALTHY ADULT MALE-VOLUNTEERS

The bioavailability and bioequivalence of three oral dosage forms of L -carnitine were studied in 15 healthy volunteers. Recently, an intrave nous (iv) dosage form of L-carnitine has been approved to be marketed in the United States. The purpose of this study was to determine after multiple dose administration of the three oral dosage forms (marketed solution, chewable tablet, and marketed tablet) the pharmacokinetics and absolute bioavailability of each of the dosage forms at steady sta te and compare them with those following administration of a single iv dose. The relative bioavailability and bioequivalence of the chewable and marketed tablet relative to the marketed solution at steady-state replicate design conditions were also studied. Bioavailability based on data that was not corrected for the baseline (uncorrected data) was compared with bioavailability determined from data corrected for base line. Steady-state conditions, based on free or total L-carnitine plas ma concentrations, were achieved by Day 3, and products were bioequiva lent based on the analysis of variance and comparisons by the two one- sided t test. Pharmacokinetic evaluations were found to be powerful to ols for bioequivalence determinations; the power to detect 20% differe nces in AUG, C-max t(max), and C-min0 was >80%. Mean absolute bioavail abilities (based on free or total L-carnitine plasma concentrations) o n Day 4 (fraction of the dose absorbed) of 'Carnitor (levocarnitine) t ablet, Carnitor (levocarnitine) oral solution, and levocarnitine chewa ble tablet relative to the first iv dose were similar to 18%. Similarl y, absolute bioavailability compared with the last iv dose was similar to 18% for all three oral formulations. However, if AUCs for oral and iv dosage forms were corrected for baseline (endogenous) plasma conce ntrations, the absolute bioavailability ranged between 14.4 and 16%, b ased on free or total L-carnitine concentrations. Based on amounts of free or total L-carnitine excreted in the urine, the three products we re also found to be bioequivalent. Correcting for baseline endogenous concentrations of L-carnitine did not significantly influence absolute bioavailability determinations.