Dosing Considerations Determined by Alterations in Physiology with Aging

The PK of each compound should be determined when one is deciding which drug candidates to use in designing formulations for the elderly. For instance, some medications have an increased half-life in older adults, either because these drugs undergo extensive hepatic metabolism (e.g., diazepam, verapamil, and pentazocine) or because they are excreted primarily by the kidneys (e.g., lithium, aminoglycosides, and digoxin) (106-112,122,150). In addition, drugs that are highly protein bound (e.g., warfarin) may be the cause of serious adverse reactions among elderly patients because of the decreased concentration of serum albumin in these patients and the subsequent rise in circulating "free" drug (106-112,118,122,150). So, if the PK behavior of the drug is known to change in elderly patients, it may be wise to avoid such drugs or to adjust the dosage accordingly. A guide has been recently published that lists a number of suggestions for dosing regimens in the geriatric patient (139).

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