Transplantation · 2000 · 71 citations · 0 references
MedicinePharmacokineticsPharmacologyHepatic PharmacokineticsHepatic PharmacotherapyPharmacodynamicsAntiviral TherapyCytochrome P450 InteractionsCytochrome P450-mediated MetabolismHepatic Drug MetabolismPharmacokinetics In Liver DiseaseViral HepatitisCyp3a4 InteractionsCytochrome P450 3A4 MetabolismCytochrome P450 IsoenzymesPharmacokinetics In Liver TransplantationPharmacokinetics In TransplantationTacrolimus InteractionsTacrolimus PharmacokineticsTacrolimus Therapeutic Drug Monitoring
A 49-year old male patient with severe hemophilia A, coinfected with HIV and HCV, who underwent orthoptic liver transplantation because of hepatitis C cirrhosis is presented. We describe a strong interaction between nelfinavir and tacrolimus postoperatively, that caused a reduction of the dose of tacrolimus by a factor 70 compared with normal, to achieve therapeutic blood concentrations and to avoid toxic side effects. We suggest that nelfinavir inhibits the metabolism of tacrolimus because both compounds are well-known substrates for the cytochrome P450 isoenzyme CYP 3A4. The nelfinavir serum concentrations were not affected by the institution of tacrolimus. Although the interaction dramatically changed the tacrolimus dose-concentration relationship, the situation was manageable by frequent monitoring of blood concentrations of tacrolimus.