6533b81ffe1ef96bd1278879

RESEARCH PRODUCT

Unusual high dose of tacrolimus in liver transplant patient, a case report.

Natale D'alessandroAlessio ProvenzaniGiovanni VizziniAdele D'antoniMonica NotarbartoloManuela LabbozzettaPaola PomaPiera Polidori

subject

AdultGraft RejectionMalemedicine.medical_specialtyATP Binding Cassette Transporter Subfamily BPharmaceutical SciencePharmacyToxicologyGastroenterologyPolymorphism Single NucleotideTacrolimusInternal medicineGenotypemedicineCytochrome P-450 CYP3AHumansPharmacology (medical)ATP Binding Cassette Transporter Subfamily B Member 1CYP3A5GenotypingPharmacologyKidneybusiness.industryGraft SurvivalHomozygoteLiver transplant patient tacrolimus dose CYP3A5 ABCB1 SNPMiddle AgedTacrolimusTissue DonorsSurgeryLiver TransplantationTransplantationsurgical procedures operativemedicine.anatomical_structurePhenotypeTreatment OutcomePharmacogeneticsToxicitySettore BIO/14 - FarmacologiaDrug MonitoringbusinessPharmacogeneticsImmunosuppressive Agents

description

Case 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.

yearjournalcountryeditionlanguage
2012-03-16International journal of clinical pharmacy
10.1007/s11096-012-9622-6https://pubmed.ncbi.nlm.nih.gov/22422348