QUINOLONE PHARMACOKINETICS IN THE ELDERLY

As a class, quinolones undergo both renal excretion and hepatic metabolism. The dominant elimination pathway is usually renal, where secretion by the proximal tubule results in renal clearances 1.5-4 times greater than creatinine clearance. The benefit of this two-pathway elimination is protection from excessive accumulation in patients with single-organ dysfunction. A number of investigations have been performed to assess how the changes in renal and hepatic function that occur in the elderly influence quinolone pharmacokinetics. For example, lomefloxacin serum concentrations are slightly higher in elderly subjects, whereas total clearance, renal clearance, and nonrenal clearance are reduced, in comparison with younger subjects. The decline in renal clearance can be explained, in part, by the parallel decline in creatinine clearance in the elderly. Dosage adjustments should not be necessary in elderly patients with only minor changes in renal function caused by age-related changes in physiology. Although the relationship between nonrenal clearance of lomefloxacin and age is slightly less precise than the relationship between total clearance and age, this may be explained by the age-related decline in hepatic function and perhaps by changes in metabolic function. Quinolones show little evidence of altered absorption or altered pharmacodynamics in the elderly. These age-related alterations in drug elimination due to normal physiologic changes are generally not significant enough to warrant changes in dosage regimens; however, disease effects, particularly alterations of renal function, appear to be more important than gradual changes in physiology characteristic of the aging population.