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• Drug Therapy in the Elderly
4

Pharmacokinetics (see Pharmacokinetics) is best defined as what the body does to the drug; it includes absorption, distribution across body compartments, metabolism, and excretion.

With aging, the metabolism and excretion of many drugs decrease, requiring that doses of some drugs be adjusted. Toxicity may develop slowly because levels of chronically used drugs tend to increase for about 5 to 6 half-lives. For example, certain benzodiazepines (diazepamSome Trade Names
VALIUM
Click for Drug Monograph
, flurazepamSome Trade Names
DALMANE
Click for Drug Monograph
, chlordiazepoxideSome Trade Names
LIBRIUM
Click for Drug Monograph
) have half-lives of up to 96 h in many elderly patients; signs of toxicity may not appear until days or weeks after therapy is started.

Absorption: Despite an age-related decrease in small-bowel surface area, slowed gastric emptying, and an increase in gastric pH, changes in drug absorption tend to be clinically inconsequential for most drugs.

Distribution: With aging, body fat generally increases, and total body water decreases. Increased fat increases the volume of distribution for highly lipophilic drugs (eg, diazepamSome Trade Names
VALIUM
Click for Drug Monograph
) and may increase their elimination half-lives.

Serum albumin decreases and α1-acid glycoprotein increases with age, but the clinical effect of these changes on serum drug binding is unclear. In patients with an acute disorder or undernutrition, rapid reductions in serum albumin may enhance drug effects because serum levels of unbound drug may increase (eg, with phenytoinSome Trade Names
DILANTIN
Click for Drug Monograph
or warfarinSome Trade Names
COUMADIN
Click for Drug Monograph
).

Hepatic metabolism: Overall hepatic metabolism of many drugs through the cytochrome P-450 enzyme system decreases with age. For drugs with decreased hepatic metabolism (see Table 1: Drug Therapy in the Elderly: Effect of Aging on Drug Metabolism* and Elimination), clearance typically decreases 30 to 40%. Theoretically, maintenance drug doses should be decreased by this percentage; however, rate of drug metabolism varies greatly from person to person, and individual titration is required.

Hepatic clearance of drugs with multistage metabolism (nonsynthetic and synthetic reactions) is more likely to be prolonged in the elderly (see Pharmacokinetics: Drug Metabolism). Usually, age does not greatly affect clearance of drugs that are metabolized by conjugation, typically with glucuronic acid.

Renal elimination: After age 30, creatinine clearance decreases an average of 8 mL/min/1.73 m²/decade; however, the age-related decrease varies substantially from person to person. Serum creatinine levels often remain within normal limits despite a decrease in GFR because the elderly generally have less muscle mass and thus produce less creatinine. Decreases in tubular function parallel those in glomerular function.

These changes decrease renal elimination of some drugs (see Table 1: Drug Therapy in the Elderly: Effect of Aging on Drug Metabolism* and Elimination). Clinical implications depend on the extent that renal elimination contributes to total systemic elimination and on the drug's therapeutic index (ratio of maximum tolerated dose to minimum effective dose). Creatinine clearance (measured or estimated using computer programs or a formula, such as Cockcroft-Gault—see Approach to the Genitourinary Patient: Creatinine clearance) is used to guide drug dosing. Because renal function is dynamic, maintenance doses of drugs should be adjusted when patients become ill or dehydrated or have recently recovered from dehydration.

Table 1
Effect of Aging on Drug Metabolism* and Elimination Class or Category Decreased Hepatic Metabolism Decreased Renal Elimination Analgesics and anti-inflammatory drugs Dextropropoxyphene IbuprofenSome Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph MeperidineSome Trade Names DEMEROL Click for Drug Monograph MorphineSome Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph NaproxenSome Trade Names ALEVE NAPROSYN Click for Drug Monograph — Antibiotics — AmikacinSome Trade Names AMIKIN Click for Drug Monograph CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph GentamicinSome Trade Names GARAMYCIN Click for Drug Monograph NitrofurantoinSome Trade Names FURADANTIN MACROBID MACRODANTIN Click for Drug Monograph StreptomycinSome Trade Names No US trade name Click for Drug Monograph TobramycinSome Trade Names NEBCIN TOBI TOBREX Click for Drug Monograph Cardiovascular drugs AmlodipineSome Trade Names NORVASC Click for Drug Monograph DiltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph LidocaineSome Trade Names XYLOCAINE Click for Drug Monograph † NifedipineSome Trade Names ADALAT PROCARDIA Click for Drug Monograph PropranololSome Trade Names INDERAL Click for Drug Monograph QuinidineSome Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph TheophyllineSome Trade Names ELIXOPHYLLIN THEO-DUR Click for Drug Monograph VerapamilSome Trade Names CALAN ISOPTIN Click for Drug Monograph N-Acetylprocainamide CaptoprilSome Trade Names CAPOTEN Click for Drug Monograph DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph EnalaprilSome Trade Names VASOTEC Click for Drug Monograph LisinoprilSome Trade Names PRINIVIL ZESTRIL Click for Drug Monograph ProcainamideSome Trade Names PROCAN SR PRONESTYL Click for Drug Monograph QuinaprilSome Trade Names ACCUPRIL Click for Drug Monograph Diuretics — AmilorideSome Trade Names MIDAMOR Click for Drug Monograph FurosemideSome Trade Names LASIX Click for Drug Monograph HydrochlorothiazideSome Trade Names ESIDRIX HYDRODIURIL Click for Drug Monograph TriamtereneSome Trade Names DYRENIUM Click for Drug Monograph Psychoactive drugs AlprazolamSome Trade Names XANAX Click for Drug Monograph † ChlordiazepoxideSome Trade Names LIBRIUM Click for Drug Monograph DesipramineSome Trade Names NORPRAMIN Click for Drug Monograph † DiazepamSome Trade Names VALIUM Click for Drug Monograph ImipramineSome Trade Names TOFRANIL Click for Drug Monograph NortriptylineSome Trade Names AVENTYL Click for Drug Monograph TrazodoneSome Trade Names DESYREL Click for Drug Monograph TriazolamSome Trade Names HALCION Click for Drug Monograph † RisperidoneSome Trade Names RISPERDAL Click for Drug Monograph Others Levodopa AmantadineSome Trade Names SYMMETREL Click for Drug Monograph ChlorpropamideSome Trade Names DIABINESE Click for Drug Monograph CimetidineSome Trade Names TAGAMET Click for Drug Monograph GlyburideSome Trade Names DIABETA GLYNASE MICRONASE Click for Drug Monograph LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph MetoclopramideSome Trade Names REGLAN Click for Drug Monograph RanitidineSome Trade Names ZANTAC Click for Drug Monograph *When aging's effect on hepatic metabolism of a drug is controversial, effects reported in the majority of studies are listed. †The effect occurs in men but not in women.

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Last full review/revision September 2009 by J. Mark Ruscin, PharmD

Content last modified September 2009