Is Palonosetron HCl Dialyzable?
No, palonosetron HCl is not dialyzable and should not be expected to be removed by hemodialysis in patients with renal impairment.
Pharmacokinetic Properties Supporting Non-Dialyzability
Palonosetron exhibits several pharmacokinetic characteristics that make it unsuitable for dialytic removal:
Large volume of distribution: Palonosetron has an extensive distribution volume of 8.34 L/kg, indicating significant tissue distribution that limits the amount of drug available in the plasma compartment for dialytic removal 1.
High protein binding: The drug demonstrates properties similar to other highly protein-bound medications, which are generally non-dialyzable 2.
Prolonged elimination half-life: The plasma elimination half-life ranges from 37 to 128 hours depending on the dose, with mean values of approximately 41.8-44.6 hours across different dosing studies 1, 3, 4. This extended half-life reflects the drug's extensive tissue distribution rather than plasma availability.
Primary Elimination Pathways
The body eliminates palonosetron through both renal and hepatic routes, but dialysis does not significantly contribute:
Renal excretion: Approximately 40% of the drug is excreted unchanged in urine, with an additional 50% excreted as metabolites (primarily M9 and M4), accounting for about 83% total urinary recovery 1.
Hepatic metabolism: The remaining drug undergoes hepatic metabolism, with only 3.4% recovered in feces 1.
Blood-to-plasma ratio: The blood-to-plasma concentration ratio of total radioactivity is 1.2, indicating minimal partitioning into erythrocytes, but the large volume of distribution means most drug resides in tissues rather than blood 1.
Clinical Implications
No dose adjustment or supplemental dosing is needed for patients on hemodialysis, as dialysis will not meaningfully remove palonosetron from the body. The drug's extensive tissue distribution and high protein binding prevent effective dialytic clearance, similar to other non-dialyzable medications like olmesartan 2.