Pharmacology: Pharmacokinetics: Intramuscular Administration: Amikacin is rapidly absorbed after intramuscular administration. In normal adult volunteers, average peak serum concentrations about 12, 16 and locally, following repeated intramuscular dosing, and when given at maximally recommended doses, no ototoxicity or nephrotoxicity has been reported.
There is no evidence of drug accumulation with repeated dosing for 10 days when administered according to recommended doses.
With normal function, 91.9% of the intramuscular dose is excreted unchanged in the urine in the first 8 hours, and 98.2% within 24 hours. Mean urine concentrations for 6 hours are 563 mcg/ml following a 250mg dose. 697 mcg/ml following a 375-mg dose, and 832 mcg/ml, following a 500-mg dose.
Preliminary intramuscular studies in newborns of different weights (less than 1.5 Kg, 1 .5 to 2.0 Kg) at dose of7.5 mg/Kg revealed that like other aminoglycosides, serum half-life values were correlated inversely with post natal age and renal clearances of amikacin. The volume of distribution of amikacin, like other aminoglycosides, remains primarily in the extracellular fluid space in neonates. Repeated dosing every 12 hours in all the above groups did not demonstrate accumulation after 5 days.
Intravenous Administration: Single doses of 500 mg (7.5 mg/kg) administered to normal adults as an infusion over a period of 30 minutes produced a peak serum concentration of 38 mcg/ml at the end of the infusion, and levels of 24 mcg/ml, 18 mcg/ml and 0.75 mcg/ml at 30 minutes, 1 hour, and 10 hours, post infusion, respectively.
Eighty four percent of the administered dose was excreted in the urine in 9 hours and about 94% within 24 hours. Repeated infusions of 7.5 mg/Kg every 12 hours in normal adults were tolerated and caused no drug accumulation.
General: Pharmacokinetic studies in normal adult subjects reveal the mean serum half-life to be slightly over 2hours with a mean total apparent volume of distribution of 24 liters (28% of the body weight). By the ultrafiltration technique, reports of protein binding range from 0 to 11 %. The Mean serum clearance rate is about100 ml/min and the renal clearance rate is 94 ml/min. in subjects with normal renal function.