A study investigating safety and pharmacokinetics of S-oxiracetam
injection in healthy volunteers
Abstract
Objective: To study the safety and pharmacokinetic (PK) profile of
S-oxiracetam (S-ORT) in healthy volunteers, so as to provide a safe and
reasonable basis for the application of formulation in phase II clinical
programs. Methods: In part 1, subjects were intravenously administered
single-ascending dose (2.0-8.0g) S-ORT. In part 2, subjects were treated
by two-sequence, two-period crossover design. In part 3, subjects were
intravenously injected with 4.0 g S-ORT once a day for 7 days. The
biological samples were collected to evaluate the PK parameters and
urine excretion rate. The safety profile of the drug was also evaluated
throughout the test process. Results: Only 1 subject displayed a mild AE
(adverse event) without obvious dosage-related AE, and SAE (serious
adverse event). Within the range of 2.0-8.0 g for a single dose, Cmax,
AUC0-t, and AUC0-∞ increased with an increase of dosage. The urine
excretion rate of the prototype drug was approximately 60%. The
consecutive administration of drug could not cause a substantial
accumulation of S-ORT. The plasma drug concentration-time curves for
both S-ORT and R-oxiracetam (R-ORT) were found to be almost identical.
Conclusions: The safety, tolerance and PK characteristics of S-ORT in
the healthy volunteers within a range of 2.0-8.0 g for a single dose, or
with 4.0 g for 7 consecutive days were found to be acceptable. The
pharmacokinetics of S-ORT and racemic oxiracetam (ORT) were observed to
be basically the same. The injection of S-ORT can be used at once-a-day
dosing regimen for Phase II clinical studies.