title: Unusual high dose of tacrolimus in liver transplant patient, a case report.
abstract: METHODS
  We describe the case of a liver transplant patient who had great difficulty in reaching the desired trough blood levels despite the use of high dose tacrolimus. The patient was homozygous for the CYP3A5*3 allele. However, the respective donor carried the wild-type CYP3A5*1/*1 genotype. Regarding ABCB1 SNPs at exon 21 and 26, the patient showed the 2677GT and 3435CC genotypes. For the corresponding donor we observed the 2677GG and 3435CC wild-type genotypes. One, two and three weeks after transplantation the patient received daily 0.219, 0.287 and 0.273 mg/kg of tacrolimus, respectively. However, the corresponding tacrolimus trough blood levels were of 4.6, 5.6 and 6.1 ng/mL. The tacrolimus target level of 10.4 ng/mL was finally reached after 1 month of therapy. During the entire period of observation the kidney showed no sign of damage. No other signs of toxicity were reported except for the occurrence of an isolated systolic hypertension.
  
  
  CONCLUSIONS
  CYP3A5 genotyping may represent a useful tool to better evaluate the appropriate initial dose of tacrolimus for patients carrying a liver with the CYP3A5*1/*1 genotype.
authors.affiliation: Department of Clinical Pharmacy, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Via E. Tricomi n. 1, 90127, Palermo, Italy. aprovenzani@ismett.edu
authors.forename: Alessio
authors.initials: A
authors.lastname: Provenzani
authors.forename: Monica
authors.initials: M
authors.lastname: Notarbartolo
authors.forename: Manuela
authors.initials: M
authors.lastname: Labbozzetta
authors.forename: Paola
authors.initials: P
authors.lastname: Poma
authors.forename: Adele
authors.initials: A
authors.lastname: D'Antoni
authors.forename: Piera
authors.initials: P
authors.lastname: Polidori
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vizzini
authors.forename: Natale
authors.initials: N
authors.lastname: D'Alessandro
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D016903:Drug Monitoring; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus