title: Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels.
abstract: We present the case of a patient with hepatitis C-induced cirrhosis and concomitant human immunodeficiency virus infection who underwent orthotopic liver transplantation. The patient developed severe, prolonged tacrolimus toxicity in the presence of human immunodeficiency virus protease inhibitors. At various times, the patient received saquinavir, ritonavir, and nelfinavir in conjunction with tacrolimus. In each instance, the tacrolimus concentration rose to toxic levels. We hypothesize that the protease inhibitors' competition for binding to cytochrome P450 isoenzyme system CYP3A induced extreme prolongation of tacrolimus metabolism. After stabilization of the patient, reinstitution of treatment with nelfinavir resulted in a >95% reduction in tacrolimus dosing from 4 mg twice per day to 0.5 mg once every 3-5 days.
authors.affiliation: Department of Medicine, New York Medical College, Valhalla, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Sheikh
authors.forename: D C
authors.initials: DC
authors.lastname: Wolf
authors.forename: E
authors.initials: E
authors.lastname: Lebovics
authors.forename: R
authors.initials: R
authors.lastname: Goldberg
authors.forename: H W
authors.initials: HW
authors.lastname: Horowitz
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000378:metabolism*; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D016559:Tacrolimus / Q000097:blood* / Q000378:metabolism* / Q000633:toxicity
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D017320:HIV Protease Inhibitors; D007166:Immunosuppressive Agents; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D016559:Tacrolimus