Abstract
Astromicin (ASTM) was administered intravenously to 4 healthy adult volunteers with an average body weight of 62kg using a continuous infusion apparatus at a constant rate of 200mg in 1 hour (Group I), 400mg in 1 hour (Group II) and 200mg in 2 hours (Group III). Concentrations of the drug in serum and urine were detemined by high power liquid chlomatography (HPLC). The mean serum concentration of the 4subjects reached the peak of 13.32μg/ml in Group I, 22.12μg/ml in Group II and 9.89μg/ml in Group III. The peak concentration was achieved at the end of infusion and was dose-related. After 8 hours, the concentration dropped to less than 1μg/ml in all groups. The urinary recovery rate was 90% in 8 hours and 95% in 24 hours. T1/2 (β) analyzed by the two-compartment open model was 1.64-1.72 hours, AUC∞was also dose-related, such as 33. 1μg·hr/ml and 31.6μg·hr/ml in Group I and Group III, and 57.6μg·hr/ml in Group II.
It is recommended for amikacin (AMK) that the peak serum concentration should not exceed 35μg/ml and the maximum concentration before the next infusion should be less than 5μg/ml. In these experiment, ASTM which is lower in toxicity than AMK did not approach 35μg/ml even at the peak level with the dosage of 400mg in 1hour. Furthermore, the excretion of the drug was fast and the serum levol of the drug became much lower than 5μg/ml very quickly. These facts indicate that ASTM should be much safer than AMK.
Judging from reported MIC values of ASTM against S. aureus and Gram-negative bacilli, effective dose levels of ASTM by intravenous drip infusion route are estimated to be 200-400mg twice a day.
