Clinical Drug Investigation

, Volume 28, Issue 7, pp 409–420

Pharmacokinetics, Safety and Tolerance of Voriconazole in Renally Impaired Subjects

Two Prospective, Multicentre, Open- Label, Parallel-Group Volunteer Studies

Authors

  • Samantha Abel
    • Pfizer Global Research and Development
  • Richard Allan
    • Pfizer Inc.
  • Kuan Gandelman
    • Pfizer Inc.
  • Konrad Tomaszewski
    • Pfizer Global Research and Development
  • David J. Webb
    • Clinical Pharmacology Unit, Centre for Cardiovascular ScienceUniversity of Edinburgh, Queen’s Medical Research Institute
  • Nolan D. Wood
    • Pfizer Global Research and Development
Original Research Article

DOI: 10.2165/00044011-200828070-00002

Cite this article as:
Abel, S., Allan, R., Gandelman, K. et al. Clin. Drug Investig. (2008) 28: 409. doi:10.2165/00044011-200828070-00002

Abstract

Background and objectives:

Since little is known regarding the pharmacokinetics of voriconazole in renally impaired patients, two prospective, open-label, parallel-group volunteer studies were conducted to estimate the effect of renal impairment on the pharmacokinetics of oral voriconazole and intravenous voriconazole solubilized with sulphobutylether-β-cyclodextrin (SBECD), respectively.

Methods:

In study A, male subjects with no (n = 6), mild (n = 6), moderate (n = 6) or severe (n = 6) renal impairment received one 200 mg dose of oral voriconazole. Voriconazole plasma levels were periodically assessed until 48 hours post-dose. In study B, male subjects with no (n = 6) or moderate (n = 7) renal impairment received multiple doses of intravenous voriconazole solubilized with SBECD (6 mg/kg twice daily [day 1] then 3 mg/kg twice daily [days 2–6] followed by a final dose of 3 mg/kg on the morning of day 7) at an infusion rate of 3 mg/kg/h. Voriconazole plasma levels were periodically assessed until 36 hours following the final dose. Pharmacokinetics were determined by non-compartmental methods.

Results:

The pharmacokinetics of voriconazole were unaffected in subjects with any degree of renal impairment in both studies. In study B, clearance of SBECD was proportional to creatinine clearance (r2 = 0.857). Although two subjects had >30% increase in serum creatinine from baseline, these changes did not correlate with SBECD trough levels (r2 = 0.053). The majority of subjects with moderate renal insufficiency were able to tolerate 7 days of intravenous voriconazole solubilized with SBECD.

Conclusion:

These data suggest that renal impairment does not affect the pharmacokinetics of voriconazole. Furthermore, in subjects with moderate renal impairment, there is a strong linear correlation between SBECD clearance and creatinine clearance, and elevated SBECD levels do not necessarily correlate with increased serum creatinine levels (an indicator of worsening renal function).

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© Adis Data Information BV 2008