The acute
toxicity and toxicity-tirnf3 dependent relations-hip of Micronomicin(MIN)and Gentamicin(GEN)were investigated in mice.The LD(5)。of MIN and GEN were 519.34 and 294.92mg/kg determined inmice with sequentlal analysis after intraneritoneal administration within13:00～15:00.Male Kun-Ming mice(n =160, weight17～24g)were housed,ten to a cage in nature light
phase and dark phase during May, with fr-ee access to food and water for 2 weeks befor experiment,80 mice weregiven intraperitoneally a single of MIN 519.34mg/kg,another 80mice were 294.92mg/kg of GEN at 01:00,07:00, 13:00, and 19:00 respectively. Theresults showed that the
highest mortality (40%)of MIN and GEN presentedat 13:00;the
lowest morlity of MIN(0%)and GEN (10%)at 07:00 and 01:00 respectively,The mortalities at different dosing times of day had sign-ificant variations.The curves xvere fitted with mean cosinor analysi;me-thod,The function of MIN xyas Y =0.1375+ 0.1489cos(15°/-192.8°) andGEN was Y=0.2250 +0.1581cos(15°/ht-213.6°),The highest mortality ofMIN was at 12: 51, GEN was at 14: 14,calculated from the functions.Theresults suggested that the LD(50) of MIN was higher 77.10% than that of GEN and toxlcity ofMIN was proved lower than that of GEN,The to-xicity of MIN and GEN depcnded on the dosing time of day with high-est toxicity during light phase and lowest during dark phase,In order to avolid or reduce the toxicity of MIN and CEN the dosage must be redesigned depending on the time of administration in clinical therapy.
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