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Pharmacokinetics of low‐dose cidofovir in kidney transplant recipients with BK virus infection
Author(s) -
Momper J.D.,
Zhao Y.,
Shapiro R.,
Schonder K.S.,
Gao Y.,
Randhawa P.S.,
Venkataramanan R.
Publication year - 2013
Publication title -
transplant infectious disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.69
H-Index - 67
eISSN - 1399-3062
pISSN - 1398-2273
DOI - 10.1111/tid.12014
Subject(s) - cidofovir , probenecid , medicine , pharmacokinetics , pharmacology , renal function , bk virus , urology , kidney , kidney transplantation , gastroenterology , immunology , virus
Background BK virus ( BKV ) infection in kidney transplant recipients is associated with progressive graft dysfunction and graft loss. Cidofovir, an antiviral agent with known nephrotoxicity, has been used in low doses to treat BKV infections. However, the systemic exposure and disposition of the low‐dose cidofovir regimen are not known in kidney transplant recipients. Methods We investigated the pharmacokinetics (PK) of low‐dose cidofovir (0.24 – 0.62 mg/kg) both without and with oral probenecid in 9 transplant patients with persistent BK viremia without nephropathy in a crossover design. Results The mean estimated glomerular filtration rate (e GFR ) of the study participants was 46.2 mL/min/1.73 m 2 (range: 17–75 mL/min/1.73 m 2 ). The contribution of active renal secretion to cidofovir total body clearance was assessed by evaluating the effect of probenecid on cidofovir PK. Maximum cidofovir plasma concentrations, which averaged approximately 1 μg/mL, were significantly below the 36 μg/mL 50% effective concentration in vitro for cidofovir against BKV . The plasma concentration of cidofovir declined with an overall disposition half‐life of 5.1 ± 3.5 and 5.3 ± 2.9 h in the absence and in the presence of probenecid, respectively ( P > 0.05). Conclusions Cidofovir clearance and e GFR were linearly related irrespective of probenecid administration ( r 2 = 0.8 without probenecid; r 2 = 0.7 with probenecid). This relationship allows for the prediction of systemic cidofovir exposure in individual patients and may be utilized to evaluate exposure‐response relationships to optimize the cidofovir dosing regimen for BKV infection.