An equation for predicting endogenous creatinine clearance (CrCl) in adults and children (with both stable and unstable renal function) from serum creatinine concentration is presented. The predictions are compared with four other available estimating methods, bases on values in 110 subjects with renal impairment of widely differing degrees. In patients with stable and with unstable renal function the corelaion between measured and predicted CrCl was better with the new equation. In patients with rapid changing renal function the new equation resulted in accurate predictions CrCl within a few hours after the change, as opposed to several with the other methods. The elimination rate constant of the aminoglycoside antibiotic amikacin correlated more precisely with CrCl values estimated from the new equation that with those measured doing 24 hr or with the other prediction methods.
The half-life of amikacin after a single intramuscular injection was determined in patients with severe renal failure who received 3.75 mg of drug/kg and in patients with various degrees of renal function who received 7.5 mg of drug/kg. The relation of the half-life of amikacin to levels of serum creatinine is practically identical to that of kanamycin. However, although concentrations of serum creatinine remained practically unchanged, rates of creatinine clearance may by considerably decreased in older subjects. This decrease may result in overestimation of the rate of glomerular filtration and subsequent overdosage. Therefore, the half-life of amikacin should be derived from values of rates of creatinine clearance or be predicted with use of a nomogram. The calculated half-life values may be used for development of appropriate dosage schedules for patients with various degrees of renal function. Such schedules would ensure therapeutic levels of drug and avoid potentially toxic accumulation of antibiotic.
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