PHARMACOKINETICS OF AMINOGLYCOSIDES WITH PARTICULAR REFERENCE TO ISEPAMICIN

The pharmacokinetic profile of the new aminoglycoside isepamicin in he althy volunteers parallels that of other molecules of the class. It is dose related within the therapeutic range (7.5 to 15 mg/kg) and is no t affected by either the route of administration (intramuscular or int ravenous) or by multiple injection. After intramuscular administration , the time to peak concentration is approximately 1.33 hours; protein binding is low, approximately 4 to 6%. After intramuscular or intraven ous administration the drug is distributed mainly to extracellular flu ids. The plasma concentration curve has a peculiar triphasic course: t he alpha-phase half-life is 0.17 hours, the beta-phase half-life is ne arly 2 hours and the gamma-phase half-life is 30 hours. The latter val ue, which is lower than the usual 100 hours for other aminoglycosides, indicates that isepamicin is less likely to accumulate in tissues. Is epamicin is not metabolically inactivated and the total dose is almost completely recovered in the urine within 24 hours. In elderly patient s a decrease in renal function might affect isepamicin clearance; this suggests the need for dosage adjustment when renal function is impair ed. The potential to cause nephrotoxicity and ototoxicity seems to be less important with isepamicin than with amikacin and gentamicin. Conc entration-dependent bactericidal activity and postantibiotic and first -exposure effect suggest that isepamicin may be administered once dail y.