Valganciclovir causes its principal dose-limiting toxicity through suppression of which cell lineage, and why does it spare infected-cell selectivity less than acyclovir?

• A Megakaryocytes, because it inhibits thrombopoietin receptors
• B Erythroid progenitors only, because it chelates iron
• C Renal tubular cells, because it accumulates via organic cation transporters
• D Bone marrow precursors generally, because ganciclovir triphosphate also inhibits host DNA synthesis ✓

Explanation

Ganciclovir is phosphorylated by the CMV UL97 kinase to ganciclovir triphosphate, which inhibits viral DNA polymerase. However, unlike acyclovir, ganciclovir triphosphate is incorporated into and inhibits host cellular DNA polymerases in dividing marrow cells, producing neutropenia and thrombocytopenia as the classic dose-limiting toxicities. Renal accumulation describes cidofovir and tenofovir rather than ganciclovir. Valganciclovir itself is simply the oral valyl ester prodrug of ganciclovir.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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