changes that occur in old age is decline in GFR (Fig. 15.1). To account for the

reduced GFR, the Cockroft and Gault Equation (see Eq. (15.3)) is widely used for

dose adjustment of drugs mainly excreted in the urine of elderly patients. This

equation is applied for dose adjustment of gentamicin, digoxin, and lithium, which

are primarily eliminated via the renal route and have narrow therapeutic margins

(McLean and Le Couteur 2004). The monitoring of GFR is very important prior to

the initiation of lithium therapy, particularly when given in the presence of comor-

bidity and polypharmacy. Ideally, lean body weight and creatinine clearance predict

steady-state lithium concentrations. The ratio of dose-serum lithium concentration

may be significantly correlated with age during chronic dosing (Vestergaard and

Schou 1984). Hence, assessment of GFR and close monitoring of therapeutic drug

levels are recommended for elderly subjects to avoid any ADRs due to declined renal

functions.

In summary, the most important PK and PD changes among the elderly are

related to ADME alterations: namely, reduced absorption of drugs from the GI

tract, decreased blood flow in liver and kidney, lesser hepatic metabolism, and

renal excretion. Age-dependent kidney hypofunction expressed by GFR steadily

declines by ageing (Fig. 15.1). While the impact of decreased GFR is highly

significant among elderly men and women, it is also substance and patient depen-

dent. Thus, there is no universal rule to calculate how to adjust drug dosing by age.

Monitoring the optimal therapeutic drug levels by the healthcare workers at least in

the dose adjustment period and in case of changes in health parameters or living

conditions would be an excellent strategy to avoid ADRs in the frail and elderly

patients. Extra precaution should be exercised for administering drugs in single

kidney patients as well as patients undergoing dialysis. Such approach would

amount to a personalized medicine. It is also important that elderly patients should

Fig. 15.1 Age-dependent GFR functions (based on cumulated data of several studies: Coresh et al.

2003; Berg 2006; Pottel et al. 2017)

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The Importance of Drug Dose Adjustment in Elderly Patients with Special. . .

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