Pharmacokinetic evaluation of a newly developed piperazine dithioctate formulation in healthy volunteers.

BACKGROUND: The formulation investigated as reference contains thioctic acid which is known to be poorly soluble in water and have some instability during storage at high temperature. To overcome these limitations, a new piperazine dithioctate (PDT) tablet formulation was developed by a domestic pharmaceutical company in Korea.

OBJECTIVE: The aim of this clinical study was to evaluate the pharmacokinetic characteristics of PDT in healthy volunteers.

METHODS: This study consisted of two clinical trials. In the part 1 study, a randomized, singledose, parallel study was performed with 24 healthy volunteers. All of the subjects were administered one of the three study formulations, Thioctacid® HR (High Release) as the reference, PDT-1 or PDT-2 (each containing thioctic acid 600 mg), respectively. To determine the harmacokinetic characteristics, blood samples were serially collected at pre-dose and at pre-defined timepoints after dosing. In the part 2 study, a randomized, single-dose, two-way crossover study was conducted with 48 subjects. All of the subjects were administered both the reference and PDT-2 formulations, with a 7-day washout period between the two medications. Blood samples were collected at the same timepoints as in the part 1 study. Tolerability was evaluated throughout the study.

RESULTS: 23 volunteers completed the part 1 study. The maximum plasma concentration (Cmax) of thioctic acid after administration of the reference tablet was 4.08 ± 2.35 μg/mL (means ± SD), and the Cmax of PDT-1 and PDT-2 was 3.53 ± 2.87 μg/mL and 4.15 ± 1.62 μg/mL, respectively. The AUClast value was 2.96 ± 1.13 μg x h/mL for the reference, 2.84 ± 1.12 μg x h/mL for PDT-1, and 3.30 ± 1.32 μg x h/mL for PDT-2. 42 volunteers completed the part 2 study. The Cmax of reference and PDT-2 was 5.59 ± 3.07 μg/mL and 5.14 ± 3.18 μg/mL, respectively. The AUClast value was 4.01 ± 1.65 μg x h/mL for the reference and 3.96 ± 1.47 μg x h/mL for PDT-2. The geometric mean ratios (PDT-2/reference) and the 90% CI for Cmax and AUClast were 0.93 (0.78 - 1.11) and 1.01 (0.94 - 1.09), respectively.

CONCLUSION: Both studies suggested that the pharmacokinetic profile of the newly developed piperazine dithioctate formulation was comparable to the pharmacokinetic profile of the reference tablet. Both study tablets were well tolerated in all of the subjects.