J05AP08 - Sofosbuvir |
Propably not porphyrinogenic |
PNP |
Rationale
Sofosbuvir has no potential for mechanism–based inhibition or clinically significant induction of CYP450 enzymes and is therefore probably not porphyrinogenic.
Chemical description
Sofosbuvir is a NS5B polymerase inhibitor.
Therapeutic characteristics
Sofosbuvir is used for the treatment of chronic HCV infection in combination with other antivials. It is administered orally.
Metabolism and pharmacokinetics
Sofosbuvir is a prodrug and is metabolized to the pharmacologically active uridine analogue triphosphate GS-461203. Sofosbuvir is not a substrate of CYP enzymes (SPC).
Induction of CYP 3A4 and 2B6 is seen in vitro, and the induction of CYP3A4 mRNA is described as weak. In vivo drug-drug interaction studies with sofosbuvir and oral contraception, antiretroviral agents, methadone, cyclosporine and tacrolimus has not uncovered any effects pointing to significant induction of CYP enzymes.
In vitro, sofosbuvir did not inhibit the activity of CYP1A2, 2B6, 2C8, 2C9, 2C19 or 2D6, and it was not a mechanism-based inhibitor of CYP 3A4 (EMA Assessment report, scientific discussion Sovaldi, Epclusa).
Sofosbuvir is not anticipated to have interaction potential with CYP enzymes (Burgess 2015, Roncero 2018, University of Liverpool).
Similar drugs
References
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