Background:

Multiple dose clinical trial was performed to evaluate the safety and pharmacokinetic profile in repetitive administration of Q-35 to healthy vluvteers.

Method:

Eight healthy volunteers were administered 200mg of Q-35 every 12hours×13times (7 days). Full pharmacokinetic studies including blood sampling and urine collection were done on day 1,4, and 7. The safety of Q-35 was checked by clinical examinations including physical examination and laboratory tests.

Results:

One of the volunteers complained of mild headache. Abdominal discomfort and diarrhea were observed in 3 of the volunteers. But all such symptoms subsided during or just after the end of the study. No abnormalities in vital sigl, laboratory tests, ECG. QEEG and slit lamp examination were observed except for AST/ALT(elevated in 3 voluteers but within normal range). In intestinal flora study, moderate decrease of CFU count was observed but was normalised 10 days after the last Q-35 administration. The mean hail-life of Q-35 in repetitive administration was 5.6±0.7 hours. similar to that of single dose administration. AUC and renal clearance(Clren) of day 1. 4, 7 were in the range of 12−14μg/ml∗hr and 110-140ml/min, respectively and there were no significant interday differences. The mean Cmax(1.7mg/L) was 5-10 times higher than the MIC90s of some typical pathogenic bacteria.

Conclusion:

The adverse effects of Q-35 in multiple dose trial to Korean volunteers were rather trivial and drug accumulation or non-linear pharmacokinctics were not observed. From these results, we concluded that Q-35 deserves Phase 2 clinical trial in Korean paients with infetious disease.