Pharmacokinetics in the elderly. Studies on ciprofloxacin.

In many ways, the elderly are a more heterogeneous group than the young, yet most pharmacokinetic studies of a new drug are carried out in healthy young volunteers. Based on a variety of age-related alterations in the gastrointestinal tract, one could postulate an a priori diminished absorption with age. In fact, absorption in old age is unchanged or even increased, as is observed with ciprofloxacin. Two comparative pharmacokinetic studies of oral ciprofloxacin found greater areas under the concentration-time curves and maximal serum concentrations in elderly than in young volunteers, which suggests better absorption (Ball et al, LeBel et al). Comparable results were also observed by Guay et al in an open study of 13 elderly patients. Smaller apparent volumes of distribution of ciprofloxacin were also noted in older than in younger volunteers. Several age-related changes in body composition may significantly affect the distribution of ciprofloxacin; the decrease in total body water plays a predominant role for this drug. For a drug that is mostly eliminated unchanged in urine, as ciprofloxacin is, the diminished glomerular filtration rate related to normal aging is the most significant factor to alter drug pharmacokinetics. A diminution of 55 to 60 percent in the total clearance of ciprofloxacin was noted in both studies comparing elderly and young persons. The decline in glomerular filtration rate observed with aging is well illustrated by the smaller renal clearance of ciprofloxacin obtained in this population. To prevent accumulation and eventual toxicity, it would seem appropriate to avoid dosage intervals shorter than 12 hours, especially in view of the lack of data concerning the effect that reduced glomerular filtration rate has on the elimination of metabolites of ciprofloxacin.