Foscarnet Pharmacokinetics in CMV Retinitis
Foscarnet is excreted mainly by the kidneys, making option (a) the correct answer. 1
Renal Elimination Profile
Foscarnet undergoes predominantly renal excretion as the unchanged drug, with renal clearance accounting for the vast majority of total systemic clearance. 1 The FDA label demonstrates that renal clearance (5.6-6.4 L/hr) comprises approximately 90% of total systemic clearance (6.2-7.1 L/hr), confirming that the kidneys are the primary route of elimination. 1
- Foscarnet clearance directly correlates with creatinine clearance, requiring mandatory dose adjustments in renal insufficiency. 1, 2
- In patients with normal renal function (CrCl >80 mL/min), foscarnet clearance is 2.13 mL/min/kg, but this drops dramatically to 0.43 mL/min/kg when CrCl falls to 10-24 mL/min. 1
- The plasma half-life increases from 1.93 hours in normal renal function to 25.3 hours in severe renal impairment, further demonstrating renal-dependent elimination. 1
Why the Other Options Are Incorrect
Blood-brain barrier penetration (option b) is actually moderate, not poor, but this does not define foscarnet's primary characteristic. 1 The CSF:plasma ratio is 0.66-0.69, indicating reasonable CNS penetration for a highly ionized compound, though this is not its distinguishing pharmacokinetic feature. 1
Intestinal absorption (option c) is extremely poor due to foscarnet's highly ionized nature. 3 Oral bioavailability is only 12-22%, which is why foscarnet must be administered intravenously—this makes option (c) false. 3
Foscarnet does not accumulate in cellular lipids (option d); instead, it accumulates in bone tissue. 1 The terminal half-life determined by urinary excretion is 87.5 hours, reflecting release from bone rather than lipid stores. 1 Postmortem data confirm bone accumulation in humans, and foscarnet binding to bone mineral (hydroxyapatite) explains the hyperphosphatemia seen in approximately one-third of patients. 4
Critical Clinical Implications of Renal Excretion
Nephrotoxicity is the major dose-limiting adverse effect, occurring in up to 30% of patients, manifesting as acute tubular necrosis. 4, 5
- Saline fluid loading during infusion can minimize renal toxicity and is essential for safe administration. 4
- The dose must be administered slowly over 2 hours (no faster than 1 mg/kg/minute) to reduce nephrotoxic risk. 4
- Serum creatinine monitoring is mandatory at least twice weekly during therapy, with immediate dose modification if renal function deteriorates. 4
Electrolyte disturbances occur in approximately one-third of patients due to foscarnet's effects on renal tubular handling of divalent cations. 4 This includes abnormalities in calcium, phosphorus, magnesium, and potassium levels, potentially leading to seizures and cardiac dysrhythmias. 4
Dosing Considerations Based on Renal Excretion
For CMV retinitis in HIV patients, the standard dose is 60 mg/kg IV every 8 hours for 14-21 days, but this requires modification in any degree of renal insufficiency. 4