Effect of renal disease and hemodialysis on foscarnet pharmacokinetics anddosing recommendations

Background: Foscarnet is an antiviral agent commonly used for managing pati ents with cytomegalovirus infection. Despite its clinical usefulness, fosca rnet is associated with substantial adverse effects including nephrotoxicit y, Moreover, foscarnet is primarily eliminated unchanged through the kidney s, thus requiring aggressive dose adjustment during kidney failure. To deve lop specific dosage guidelines, information on the disposition of this comp ound 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 fi ve groups depending on their degree of renal dysfunction, Group I included subjects with normal renal function; group 5 included subjects requiring ma intenance hemodialysis. Nondialysis study subjects received a single 60-mg/ kg intravenous dose of foscarnet whereas hemodialysis subjects received two intravenous doses, separated by I week, to compare the effects of conventi onal 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 indic ated 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 o n dialysis. Foscarnet dialysis clearance (based on dialysate recovery) aver aged 183 ml/minute with conventional dialysis methods and 253 ml/minute dur ing high-nux 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 b e made in renal failure patients. Therefore, a patient-specific dosage nomo gram has been developed.