PHARMACOKINETICS OF ISEPAMICIN

Isepamicin is a new aminoglycoside that has activity against many bact eria resistant to other aminoglycosides. The pharmacokinetics of isepa micin have been characterized in neonatal, pediatric, adult, elderly a nd renally impaired human populations as well as in clinical trials us ing the techniques of population pharmacokinetics. The pharmacokinetic s of isepamicin are uncomplicated and generally similar to those of ot her aminoglycosides, although there is some evidence that it may have less tissue accumulation. The drug is completely absorbed following in tramuscular administration. The drug is not metabolized and unchanged isepamicin accounts for all of the drug substance in plasma and urine. It is completely eliminated via the renal route; consequently dosing in patients with renal insufficiency has to be adjusted according to t he degree of renal impairment. The pharmacokinetics of isepamicin are generally linear. Thus peak plasma concentrations and area under the p lasma concentration curve (AUG) values are proportional to the adminis tered dose while clearance (1.1-1.3 mL/min/kg), volume of distribution at steady state (0.23-0.29 L/kg) and half-life (2-2.5 h) are independ ent of dose. There is no significant accumulation of drug in the plasm a with once- or twice-daily dosing. The isepamicin plasma concentratio n curve following a 1 g intravenous dose to healthy volunteers can be best characterized by a tri-exponential curve corresponding to a t1/2 alpha of 0.17 h, a t1/2 beta of 2.1 h, and a gamma-phase of 34 h. The t1/2 beta represents the elimination phase and changes with age and re nal function, while the gamma-phase represents the return of drug to p lasma from a deep compartment including binding in renal tissue. The g amma-phase represents less than 3% of the total AUC and does not chang e with age. Isepamicin readily distributes to extracellular fluid and pulmonary tissue. In conclusion, isepamicin demonstrates predictable l inear kinetics and is similar pharmacokinetically to other aminoglycos ides. Preliminary indications of decreased tissue accumulation implied from pharmacokinetic data need to be evaluated further. The pharmacok inetic and pharmacodynamic characteristics of isepamicin favour once-d aily dosing.