Pharmacokinetic Approach to Drug Dosing in the Aged

Abstract

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.

Population Pharmacokinetic Analysis of Bisoprolol

“…This relationship has not previously been described in the literature; it is displayed graphically in figure 2. It is known in general terms that renal function deteriorates with increasing age (Ritschel 1976). In the case of bisoprolol, where it is claimed that CL is balanced between the renal and hepatic routes (Leopold 1986), one would expect either that age would have no influence on CL, or that CL would be reduced in the elderly.…”

Analysis of drug adverse events in elderly patients based on the Japanese Adverse Drug Event Report Database

“…The age cut-off for AEs was set to 80 years, which is the age at which many concomitant drugs are often taken and a time when the decline in renal function is particularly noticeable. 3 The risk of AEs was evaluated using the reporting odds ratio (ROR) for patients aged 80 years or older compared with those aged less than 80 years old. ROR > 1 was considered a significant difference in patients aged 80 years or older.…”

“…Moreover, the combined use of six or more drugs increases the risk of occurrence of adverse events (AEs) 2 . In addition, renal function deteriorates markedly with age, and the efficiency of creatinine clearance is 50% lower in patients aged 80 years or older compared with those under 50 years of age, 3 which results in high drug exposure among the elderly. Thus, the risk of AEs resulting from drug interactions and pharmacokinetic changes associated with decreased physiological function is noteworthy, and these characteristics of the elderly should be considered in the context of pharmacotherapy.…”

Gabapentin in Geriatric Mania

“…[1][2][3][4] In elderly manic patients, the therapeutic window for mood stabilizer medications such as lithium and carbamazepine is narrow, and it is often difficult to treat mania effectively without causing toxicity. 5 Hence, atypical antipsychotic and anticonvulsant medications play a more important role in the treatment of elderly manic patients.…”