Table 1.

Changes in pharmacokinetic factors associated with aging and potential effects on antimicrobial dosing

PK parameter	Considerations in elderly patients	Impact on drug pharmacokinetics	Potential effects on antimicrobial dosing	Example(s)	References
Absorption	Decreased gastric acid production	Impaired drug dissolution	Decreased bioavailability of drugs	Azithromycin, erythromycin, cefaclor, ceftibuten, itraconazole, ketoconazole, sulfonamides, dapsone, pyrimethamine, atazanavir	12, 14, 15
	Decreased gastric motility Decreased small bowel surface area Decreased splanchnic blood flow	Decreased absorption of drugs	Standard dose may be inadequate	Cefpodoxime proxetil	11
Distribution	Increased proportion of adipose tissue	Increased distribution of lipid-soluble drugs	Prolonged lipid-soluble drug half-life	Rifampin, fluoroquinolones, macrolides, oxazolidinones, tetracyclines, amphotericin B, imidazole antifungals	19, 20
	Decreased lean body mass Decreased total body water	Decreased distribution of water-soluble drugs	Increased plasma concentration	Aminoglycosides, glycopeptides, beta-lactams	19, 20
	Increased plasma alpha-1-acid glycoprotein levels	Decreased free concentration of basic antimicrobials	Standard dose may be inadequate	Macrolides	21
	Water accumulation near infection site (edema, ascites)	Decreased concentration of hydrophilic drugs in plasma and at site of infection	Standard dose may be inadequate		22
	Malnutrition/proteinuria leading to hypoalbuminemia	Increased concentration of free drug	Drug toxicity	Penicillins, ceftriaxone, sulfonamides, clindamycin	19, 21, 22, 25
Metabolism	Liver disease; normal physiological effects of aging on the liver	Decreased hepatic blood flow Decreased P450 CYP enzyme activity	Prolonged drug half-life of hepatically metabolized drugs	Macrolides, fluoroquinolones, azole antifungals, antiretrovirals	21, 25, 27
	Polypharmacy	Competition for CYP P450 hepatic enzymes	Variable drug activity	Macrolides, fluoroquinolones, azole antifungals, antiretrovirals	21, 25, 27
Elimination	Decreased renal function/renal disease	Decreased renal blood flow Decreased glomerular filtration rate Decreased drug removal	Prolonged drug half-life Accumulation of drug in plasma High serum concentrations Increased risk of toxicity	Beta-lactams, glycopeptides, aminoglycosides, daptomycin, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole	31
	Renal replacement therapy	Increased drug removal	Dose adjustment required		32

Abbreviation: PK, pharmacokinetic.