Table 1.
Pharmacokinetic parameter | Definition | Influenced by | Examples of changes in chronic kidney disease | Impact of those changes |
---|---|---|---|---|
Absorption | A determinant of drug bioavailability, representing the amount of administered dose reaching systemic circulation | • Gastric pH • Gastrointestinal motility • First-pass metabolism |
• Increased gastric pH (conversion of high salivary urea concentrations into ammonia by gastric urease) • Delayed gastric emptying in patients with concomitant diabetic gastroparesis • Gastrointestinal edema occurring in patients with concomitant cirrhosis or congestive heart failure |
• Impacts the time required to reach maximal plasma concentration • Decreases maximum plasma concentration |
Volume of distribution | The extent of drug distribution throughout the body; especially the amount of drug distributed into extravascular tissues | • Plasma protein binding • Tissue binding • Total body water |
• Hypoalbuminemia • Increased concentrations of alpha-1-acid glycoprotein • Fluid retention, increasing total body water |
• Impacts concentration of free drug available to bind to receptors • Increased volume of distribution for hydrophilic drugs |
Elimination | The extent of drug clearance either renally or nonrenally | • Renal: number of functioning nephrons, renal blood flow, glomerular filtration rate, and tubular secretion • Nonrenal: hepatic and extrahepatic metabolism (cytochrome P450, UGT, and NAT enzymes), and transport pathways |
Renal • Decreased amount of functioning nephrons • Reduced renal blood flow • Reduced glomerular filtration rate • Reduced tubular secretion Nonrenal • Decreased activity of cytochrome P450, UGT, and NAT • Cytochrome P450 3A4 downregulation via direct inhibition by uremic toxins |
• Diminished overall elimination leading to overall drug accumulation |