Pharmacokinetic approach to drug dosing in the aged.

Data in the literature show that there is a constant ratio of total body fluid to lean cell mass with increasing age (1.15 for males and 1.31 for females). Since the drug receptors usually are found in the tissues, and since cell mass and total body fluid apparently decrease at a constant rate, it would seem that the volume of distribution of drugs decreases proportionally with increasing age. Kidney function, as measured by the glomerular filtration rate and transport maximum, apparently decreases with increasing age according to zero-order kinetics. Based on these data, correction factors were established for the change in volume of distribution and renal functions with increasing age. Equations were derived for calculating the loading dose and maintenance dosage of drugs in multiple-dose therapy in females and males. Equations are presented for drugs following the minimal inhibitory concentration (MIC) pattern and the log dose-response pattern, respectively. The MIC pattern is recommended in the use of bacteriostatic drugs, for which it is essential to maintain recommended in the use of bacteriostatic drugs, for which it is essential to maintain during the entire course of therapy a minimum inhibitory concentration. The log dose-response pattern is recommended for bactericidal and antiarrhythmia drugs, for which it is essential to obtain an average therapeutic steady-state concentration. Based on this pharmacokinetic approach, it would seem that elderly patients, during multiple-dose therapy, are exposed to dose sizes that are too large if no correction is made.