Renally excreted drugs

Introduction

Renal function declines with age as a result of the anatomical and physiological changes that occur with aging. Because renal function deteriorates with age, even in the seemingly healthy patient, clearance of renally excreted and metabolized drugs may be markedly impaired in the elderly patient. Therefore, to avoid toxic effects a dosage reduction is often necessary.

Because both the production and excretion of creatinine decreases with age, an elderly patient can have markedly decreased renal function without having an elevated serum creatinine level. Thus, an estimate of creatinine clearance is necessary for determining the appropriate dosage of renally excreted drugs. Creatinine clearance can either be measured by a timed urine collection or estimated from serum creatinine. Several methods have been developed for calculating creatinine clearance. The method of Cockcroft and Gault as modified by Jelliffe has been found to be as accurate as a timed urine collection and much more convenient.

Dosage adjustment guidelines which are based on creatinine clearance have been published. Also, manufacturers often provide dosage guidelines in the package insert which are based on creatinine clearance.

A dosage regimen may be adjusted either by lowering the dose or prolonging the dosage interval. The dosage reduction method is recommended for those drugs for which a relatively constant blood level is desired and for antibiotics without a post-antibiotic effect.  For drugs which require a "washout" period and for antibiotics without a post-antibiotic effect, the interval extension method is recommended.

See also:

Monitoring parameters

Precautions

Pharmacokinetic formulas

Other creatinine clearance methods

Bibliography