Pharmacokinetics and safety of intravesicular cidofovir in allogeneic HSCT recipients.

Published

Journal Article

OBJECTIVES: The objective of this study was to evaluate the pharmacokinetics and safety of cidofovir administered via the intravesicular route to patients with haemorrhagic cystitis following allogeneic HSCT (allo-HSCT). METHODS: Patients with gross haematuria and confirmed BK or adenovirus viruria following allo-HSCT were prospectively enrolled in an open-label pharmacokinetic study (ClinicalTrials.gov registration: NCT01816646). Three hours after an oral probenecid dose (2 g), cidofovir (2.5-5 mg/kg in 50-100 mL of normal saline) was given via a transurethral catheter for up to 2 h of dwell time. Serial plasma samples were obtained over 24 h and assayed for cidofovir concentrations using LC-MS/MS. A custom pharmacokinetic model with a time-limited absorption compartment was fitted to the concentration-time profile of each patient. Systemic drug exposure was expressed as AUC0-24, by integrating the best-fit profile with respect to time. RESULTS: Six subjects (mean ± SD age = 38 ± 21 years) with baseline serum creatinine <1.4 mg/dL were enrolled. Mean values for volume of distribution, clearance and elimination half-life were 19.5 L, 5.6 L/h and 2.8 h, respectively. Compared with the reported AUC0-24 for an equivalent intravenous dose, intravesicular instillation of cidofovir resulted in 1%-74% of the corresponding systemic exposure. Owing to primarily lower abdominal pain, only two patients were able to tolerate a 2 h dwell time. One patient developed a >50% increase in serum creatinine within 7 days of administration. CONCLUSIONS: Intravesicular administration of cidofovir resulted in highly variable systemic exposures. The safety and efficacy of intravesicular cidofovir should be further evaluated before routine use.

Full Text

Duke Authors

Cited Authors

  • Aitken, SL; Zhou, J; Ghantoji, SS; Kontoyiannis, DP; Jones, RB; Tam, VH; Chemaly, RF

Published Date

  • March 2016

Published In

Volume / Issue

  • 71 / 3

Start / End Page

  • 727 - 730

PubMed ID

  • 26612873

Pubmed Central ID

  • 26612873

Electronic International Standard Serial Number (EISSN)

  • 1460-2091

Digital Object Identifier (DOI)

  • 10.1093/jac/dkv393

Language

  • eng

Conference Location

  • England