Impact of glomerular kidney diseases on the clearance of drugs.
Numerous physiologic variations, including urinary protein excretion, low serum albumin concentrations, and reductions in kidney function (clearance), exist in patients with glomerulonephritis. These factors could alter the disposition of numerous drugs. The purpose of the current article was to review the influence of glomerulonephritis on the pharmacokinetics of drugs used clinically or experimentally in the treatment of these conditions. Several articles or presentations were located that reported on the pharmacokinetics of immunosuppressant, cytotoxic, and therapeutic antibody drugs in populations with glomerulonephritis. Most publications reported an increase in systemic clearance in glomerulonephritis as compared with populations in whom the drugs were typically used and in patients with nonglomerular forms of chronic kidney disease. It appears that the increase in systemic clearance is predominantly through nonrenal clearance pathways, although enhancement of renal clearance has also been appreciated for some drugs. Available preliminary data suggest specific alterations in the activity of individual pathways of drug metabolism and transport. Recommendations are provided for the design of future studies of drugs in the glomerulonephritis population and for inclusion of patients with urinary protein excretion in studies that assess drug pharmacokinetics.
Division of Nephrology and Hypertension, Department of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, CB 7155, 7005 Burnett Womack Building, Chapel Hill, NC 27599-7155, USA. Melanie_Joy@med.unc.edu
Melanie S
MS
Joy
D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics