[Safety and pharmacokinetics of 400 and 600 mg arbekacin sulfate to healthy male volunteers].

Abstract

We assessed the safety and pharmacokinetics of arbekacin sulfate (ABK, brand name: Habekacin injection) in single and 7-day multiple administration of ABK 400 and 600 mg as potency to healthy male volunteers. In the single administration of ABK 400 and 600 mg (over 30 min, drip infusion), C(max) values were 41.0 +/- 3.6 microg/mL and 63.0 +/- 9.9 microg/mL, respectively. Serum ABK concentrations at 60 min (C(peak)) after the start of administration were 23.2 +/- 2.9 microg/mL and 38.5 +/- 3.3 microg/mL, respectively, and the mean serum ABK concentrations at 24 hr (C(trough)) after the start of administration were less than 0.4 microg/mL (LOQ: limited of quantitation). C(max), Cpeak and AUC(0-infinity) were increased with doses, and t1/2, CL(tot), CL(r) V(ss) and urinary excretion were comparable at both doses. In the multiple administration of ABK 400 and 600 mg (over 30 min, drip infusion) once a day for 7 days, C(max0, C(peak) and AUC(0-infinity) were comparable from the 1st day through to 7th day and increased with doses. After the administration, the serum ABK concentrations were decreased with time, and the means of C(trough) were 0.4 microg/mL (LOQ) -0.5 microg/mL, which showed ABK has no tendency toward accumulation. In addition, t1/2, CL(tot), CL(r) V(ss) and urinary excretion were constant throughout administration days at either dose, and CL(tot) containing CL(r) was not decreased. There were no notable changes in the functions of the kidney, auditory organs, etc. Based on the above-mentioned results, when ABK 400 or 600 mg was intravenously administered over 30 min once or once a day for 7 days to the healthy male volunteers with normal renal clearance, it is suggested there were no problems in terms of safety, and C(max) were 36.7-54.1 and 44.2-78.5 microg/mL, respectively. In addition, C(trough) was 0.5 microg/mL or lower at either doses and ABK was not accumulated in multiple administration of ABK. ABK was, therefore, expected to have good safety profile and favorable pharmacokinetics.