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Pharmacokinetics of cidofovir in renal insufficiency and in continuous ambulatory peritoneal dialysis or high‐flux hemodialysis
Author(s) -
Brody Suzanne R.,
Humphreys Michael H.,
Gambertoglio John G.,
Schoenfeld Patricia,
Cundy Kenneth C.,
Aweeka Francesca T.
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1999.3
Subject(s) - medicine , continuous ambulatory peritoneal dialysis , cidofovir , pharmacokinetics , hemodialysis , volume of distribution , urology , peritoneal dialysis , dialysis , renal function , probenecid , immunology , virus
Background Cidofovir is an antiviral agent used for the treatment of cytomegalovirus infection in patients with acquired immunodeficiency syndrome. Because cidofovir is primarily eliminated by the kidneys and because its main adverse effect is nephrotoxicity, an understanding of the pharmacokinetic disposition of cidofovir in patients with renal insufficiency is necessary. Methods Twenty‐four subjects were enrolled into this study and were divided into 6 groups depending on their degree of renal dysfunction, including subjects receiving maintenance continuous ambulatory peritoneal dialysis and high‐flux hemodialysis. The creatinine clearance (CL CR ) for subjects not receiving dialysis ranged from 12 to 164 mL/min. Each subject received a single 0.5 mg/kg intravenous dose of cidofovir over 1 hour. Subjects not receiving dialysis were given intravenous hydration with 1 L normal saline solution and concomitant oral probenecid. Serial serum and urine samples were collected to determine pharmacokinetic parameters with use of noncompartmental methods. Results Mean ± SD cidofovir clearance (CL) in control subjects (normal renal function; n = 5) was 1.7 ± 0.1 mL/min/kg, which decreased with declining renal function as indicated by the regression equation: CL (mL/min/kg) = 0.94 × CL CR (mL/min/kg) + 0.064 ( r 2 = 0.91). Mean volume of distribution at steady state did not change significantly in subjects with kidney disease and cidofovir serum elimination half‐life was significantly increased in subjects with severe renal impairment. Cidofovir was not significantly cleared during continuous ambulatory peritoneal dialysis, but high‐flux hemodialysis resulted in the removal of 52% ± 11% of the dose administered. Conclusion The significant ( P < .001) correlation observed between CL CR and CL in subjects with varying degrees of renal insufficiency indicates that aggressive dosage reduction of cidofovir would be necessary in subjects with kidney disease to ensure comparable drug exposure based on serum levels. Clinical Pharmacology & Therapeutics (1999) 65 , 21–28; doi: 10.1038/cptclpt.1999.3