Quinolone disposition in the elderly. Practical implications.

Abstract

The fluoroquinolones are antibiotics frequently used in infections that affect elderly individuals. The physiological aging process can profoundly affect the pharmacokinetics of drugs, necessitating adjustment of dosage regimens in the elderly. Changes in pharmacokinetics with age are mainly due to the progressive deterioration of renal function, with resultant lower clearance of drugs which are eliminated by the kidneys. Ofloxacin is almost totally renally excreted and elimination is slower in older age groups; a dose reduction is therefore recommended for this quinolone. Unexpected alterations in pharmacokinetics may occur, as exemplified by the increased bioavailability of oral ciprofloxacin in elderly subjects. This is a well-documented phenomenon of such significance that lower oral doses are advisable for the elderly. Renal clearance of ciprofloxacin decreases in old age, but because of substantial nonrenal elimination the total clearance is affected less. Studies of the pharmacokinetics of the other quinolones in old age are scarce. No data exist on the absolute oral bioavailability of norfloxacin, enoxacin and pefloxacin. Renal clearance seems to be reduced, but since no intravenous studies have been reported, the total and nonrenal clearances are unknown in the elderly. No safe conclusions can be drawn regarding the necessity of dose reductions from a pharmacokinetic point of view. However, reports of adverse reactions to quinolones in the elderly, especially concentration-dependent symptoms from the central nervous system, and the risk of interaction with other drugs, suggest the need for caution in determining dosages of all of these compounds in elderly subjects.