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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, and the physiologic changes of aging require dose adjustment for some drugs. Toxicity may accumulate slowly because levels of chronically used drugs tend to increase for about 6 half-lives. For example, certain benzodiazepines ( diazepam Some Trade Names
VALIUM
Click for Drug Monograph
, flurazepam Some Trade Names
DALMANE
Click for Drug Monograph
, chlordiazepoxide Some 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 and an increase in gastric pH, changes in drug absorption tend to be trivial and clinically inconsequential.

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

Serum albumin decreases and α₁-acid glycoprotein increases with aging, 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.

Hepatic metabolism: Overall hepatic metabolism of many drugs through the cytochrome P-450 enzyme system decreases with aging. 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.

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 Ibuprofen Some Trade Names ADVIL MOTRIN NUPRIN Click for Drug Monograph Meperidine Some Trade Names DEMEROL Click for Drug Monograph Morphine Some Trade Names DURAMORPH MS CONTIN MSIR ROXANOL Click for Drug Monograph Naproxen Some Trade Names ALEVE NAPROSYN Click for Drug Monograph — Antibiotics — Amikacin Some Trade Names AMIKIN Click for Drug Monograph Ciprofloxacin Some Trade Names CILOXAN CIPRO Click for Drug Monograph Gentamicin Some Trade Names GARAMYCIN Click for Drug Monograph Nitrofurantoin Some Trade Names FURADANTIN MACROBID MACRODANTIN Click for Drug Monograph Streptomycin Some Trade Names No US trade name Click for Drug Monograph Tobramycin Some Trade Names NEBCIN TOBI TOBREX Click for Drug Monograph Cardiovascular drugs Amlodipine Some Trade Names NORVASC Click for Drug Monograph Diltiazem Some Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph Lidocaine Some Trade Names XYLOCAINE Click for Drug Monograph † Nifedipine Some Trade Names ADALAT PROCARDIA Click for Drug Monograph Propranolol Some Trade Names INDERAL Click for Drug Monograph Quinidine Some Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph Theophylline Some Trade Names ELIXOPHYLLIN THEO-DUR Click for Drug Monograph Verapamil Some Trade Names CALAN ISOPTIN Click for Drug Monograph N-Acetylprocainamide Captopril Some Trade Names CAPOTEN Click for Drug Monograph Digoxin Some Trade Names DIGITEK LANOXIN Click for Drug Monograph Enalapril Some Trade Names VASOTEC Click for Drug Monograph Lisinopril Some Trade Names PRINIVIL ZESTRIL Click for Drug Monograph Procainamide Some Trade Names PROCAN SR PRONESTYL Click for Drug Monograph Quinapril Some Trade Names ACCUPRIL Click for Drug Monograph Diuretics — Amiloride Some Trade Names MIDAMOR Click for Drug Monograph Furosemide Some Trade Names LASIX Click for Drug Monograph Hydrochlorothiazide Some Trade Names ESIDRIX HYDRODIURIL Click for Drug Monograph Triamterene Some Trade Names DYRENIUM Click for Drug Monograph Psychoactive drugs Alprazolam Some Trade Names XANAX Click for Drug Monograph † Chlordiazepoxide Some Trade Names LIBRIUM Click for Drug Monograph Desipramine Some Trade Names NORPRAMIN Click for Drug Monograph † Diazepam Some Trade Names VALIUM Click for Drug Monograph Imipramine Some Trade Names TOFRANIL Click for Drug Monograph Nortriptyline Some Trade Names AVENTYL Click for Drug Monograph Trazodone Some Trade Names DESYREL Click for Drug Monograph Triazolam Some Trade Names HALCION Click for Drug Monograph † Risperidone Some Trade Names RISPERDAL Click for Drug Monograph Others Levodopa Amantadine Some Trade Names SYMMETREL Click for Drug Monograph Chlorpropamide Some Trade Names DIABINESE Click for Drug Monograph Cimetidine Some Trade Names TAGAMET Click for Drug Monograph Lithium Some Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph Ranitidine Some 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.

Hepatic clearance of drugs with multistage metabolism (nonsynthetic and synthetic reactions) is more likely to be prolonged in the elderly (see Pharmacokinetics: 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, interindividual variation in the decline with aging is substantial. Serum creatinine levels often remain within normal limits despite a decrease in GFR because the elderly 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—see Approach to the Genitourinary Patient: Creatinine clearance) is used to guide drug dose. Because renal function is dynamic, maintenance doses of drugs should be adjusted when patients become ill, dehydrated, or have recently recovered from dehydration.

Last full review/revision November 2005

Content last modified November 2005