Findings from a Phase I study published in the American College of Clinical Pharmacology showed that patients with renal impairment experience reduced clearance of doxecitine and doxribtimine compared with healthy controls. However, no notable safety concerns were identified after a single dose.
The U.S. Food and Drug Administration approved doxecitine and doxribtimine for patients with thymidine kinase 2 deficiency (TK2d) in November 2025, making it the first and only drug approved for patients with the disease. Together, doxecitine and doxribtimine increase the level of deoxycytidine (dC) and deoxythymidine (dT), which are needed to build mitochondrial DNA.
Previous studies have suggested that the kidneys are responsible for clearing dC and dT from the body. “It is of interest to determine whether renal impairment adversely affects the overall clearance of dC and dT, particularly during long-term administration in the setting of TK2d therapy,” the authors explained.
The study included eight individuals with severe renal impairment, eight with moderate renal impairment and 16 healthy controls. All participants received one dose of doxecitine and doxribtimine as a powder, which they mixed with juice or water.
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Levels of dC and dT in the bloodstream directly after dosing were higher in those with renal impairment than controls. While dC levels peaked between 45 minutes 1.5 hours after dosing, dT levels peaked between 45 minutes and 1 hour. However, there was no association between level of kidney impairment and dC or dT exposure.
In addition, statistical analysis revealed a weak negative relationship between estimated glomerular filtration rate (eGFR) and dC and dT exposure. This suggests that those with poorer kidney function had slightly greater systemic exposure to dC and dT.
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