title: Use of rapamycin in a transplant patient who developed cyclosporin neurotoxicity.
abstract: We describe the case of a paediatric kidney transplant patient who developed cyclosporin neurotoxicity on day 7 post-transplant. Consequently, her cyclosporin was stopped and she was commenced on rapamycin. Over the next 3 weeks her creatinine remained elevated and she had several episodes of biopsy proven rejection, despite increasing the initial dose of rapamycin by tenfold. Her whole blood rapamycin levels also remained well below the target range of 10-20 ng/ml. On day 38 post-transplant, the decision was made to add tacrolimus to her immunosuppression. At the same time, phenytoin, which had been commenced during her episode of cyclosporin neurotoxicity, was withdrawn. After this point her rapamycin blood levels rapidly increased to within the therapeutic range and she improved clinically. We propose that phenytoin, as a p450 cytochrome enzyme inducer, increased the metabolism of rapamycin in this patient and hence decreased the initial therapeutic effectiveness of this drug.
authors.affiliation: University Department of Surgery, Western Infirmary, Glasgow, UK. cbhodges3@aol.com
authors.forename: C B
authors.initials: CB
authors.lastname: Hodges
authors.forename: H
authors.initials: H
authors.lastname: Maxwell
authors.forename: T J
authors.initials: TJ
authors.lastname: Beattie
authors.forename: A V
authors.initials: AV
authors.lastname: Murphy
authors.forename: R M
authors.initials: RM
authors.lastname: Jindal
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects; D002648:Child; D016572:Cyclosporine / Q000009:adverse effects*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000601:surgery; D010672:Phenytoin / Q000009:adverse effects; D012640:Seizures / Q000139:chemically induced; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D007166:Immunosuppressive Agents; D010672:Phenytoin; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D020123:Sirolimus