Effect of renal disease and hemodialysis on foscarnet pharmacokinetics and dosing recommendations.

Abstract

BACKGROUND:

Foscarnet is an antiviral agent commonly used for managing patients with cytomegalovirus infection. Despite its clinical usefulness, foscarnet is associated with substantial adverse effects including nephrotoxicity. Moreover, foscarnet is primarily eliminated unchanged through the kidneys, thus requiring aggressive dose adjustment during kidney failure. To develop specific dosage guidelines, information on the disposition of this compound in patients with varying degrees of renal function and those requiring dialysis is essential.

DESIGN:

Twenty-six subjects were enrolled in this study and divided into five groups depending on their degree of renal dysfunction. Group 1 included subjects with normal renal function; group 5 included subjects requiring maintenance hemodialysis. Nondialysis study subjects received a single 60-mg/kg intravenous dose of foscarnet whereas hemodialysis subjects received two intravenous doses, separated by 1 week, to compare the effects of conventional and high-flux dialysis methods.

RESULTS:

Mean plasma clearance in control subjects averaged 2.1+/-0.7 ml/minute/kg and declined proportionally with changing renal function as indicated by the regression equation: Clp (ml/minute/kg) = 1.48 [CrCl (ml/minute/kg)]-0.08 (r2 = 0.82). Mean half-life averaged 1.9+/-0.1 hours in normal subjects and increased to a mean of 25+/-19 hours in study subjects with severe impairment not on dialysis. Foscarnet dialysis clearance (based on dialysate recovery) averaged 183 ml/minute with conventional dialysis methods and 253 ml/minute during high-flux procedures, which resulted in removal of 37% and 38% of a dose for the two methods, respectively.

CONCLUSIONS:

These data indicate that substantial dosage adjustments must be made in renal failure patients. Therefore, a patient-specific dosage nomogram has been developed.

• Authors: F T Aweeka, M A Jacobson, S Martin-Munley, A Hedman, P Schoenfeld, R Omachi, S Tsunoda, J G Gambertoglio
• Journal: Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association (J Acquir Immune Defic Syndr Hum Retrovirol) Vol. 20 Issue 4 Pg. 350-7 (Apr 01 1999) ISSN: 1077-9450 [Print] United States
• PMID: 10096579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Foscarnet

Topics

• Adult
• Aged
• Dose-Response Relationship, Drug
• Female
• Foscarnet (pharmacokinetics)
• Health Planning Guidelines
• Humans
• Kidney Diseases
• Male
• Middle Aged
• Renal Dialysis