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


METHODS
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.
Aweeka
F T
FT
Department of Clinical Pharmacy, University of California, San Francisco 94143-0622, USA. aweeka@itsa.ucsf.edu
Jacobson
M A
MA
Martin-Munley
S
S
Hedman
A
A
Schoenfeld
P
P
Omachi
R
R
Tsunoda
S
S
Gambertoglio
J G
JG
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D017245:Foscarnet / Q000493:pharmacokinetics*; D006287:Health Planning Guidelines; D006801:Humans; D007674:Kidney Diseases; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
D017245:Foscarnet