Table 2.

Changes in pharmacokinetic parameters in patients with chronic kidney disease [14, 15, 16, 17, 18, 20]

Pharmacokinetic parameter	Definition	Influenced by	Examples of changes in chronic kidney disease	Impact of those changes
Absorption	A determinant of drug bio-availability, 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 extra-hepatic 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

Created by Bettinger JJ, Mathew RO, Wegrzyn EL, Fudin J. Updated November 2016: With permission, Dr. Jeffrey Fudin http://paindr.com/wp-content/uploads/2018/02/2016Nov-Changes-in-pharmacokinetic-parameters-in-patients-with-CKD-1.pdf. Data compiled from [14, 15, 16, 17, 18, 20]. UGT, UDP-glucuronosyltransferase; NAT, N-acetyltransferase.