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.
(248/250 words)