TABLE 1.

Experimental groups, conditions of treatments, and relevance to the clinical use of aminoglycosides

Drug	Dose (mg/kg)a	Duration (days)	Fold increase over:
			Clinical doseb	Clinical daily drug exposurec
Gentamicin	10	4–10	∼2	∼0.5
	20	4–10	∼4	∼1
Netilmicin	10	4–10	∼1.7	∼0.4
	20	4–10	∼3.3	∼0.8
Amikacin	40	10	∼2.7	∼0.7
Isepamicin	40	10	∼2.7	∼0.7

^aTwice-a-day schedule (daily dose split into two administrations at 12-h intervals). This schedule (or even a three-times-a-day schedule) was long considered mandatory for aminoglycosides but is known to increase toxicities at both low and high doses in animals (38, 52). Data for patients are less definite, even though a trend toward less toxicity is commonly observed with a once-a-day schedule (21, 48). 

^bSuggested maintenance doses for an adult patient with an estimated creatinine clearance of 90 ml/min (20) (gentamicin, 5.1; netilmicin, 6; and amikacin, 15 mg/kg, respectively) or based on the registered dosage in Belgium and many other countries for isepamicin. 

^cBased on estimated ratio of areas under the serum concentration-time curve, AUC ratio, using the dose ratio defined in footnote b and assuming apparent half-lives of ∼30 min in rats and ∼120 min in humans (β-elimination phases).