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.
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.
Authors: R B Kim; B F Leake; E F Choo; G K Dresser; S V Kubba; U I Schwarz; A Taylor; H G Xie; J McKinsey; S Zhou; L B Lan; J D Schuetz; E G Schuetz; G R Wilkinson Journal: Clin Pharmacol Ther Date: 2001-08 Impact factor: 6.875
Authors: Iain A M Macphee; Salim Fredericks; Tracy Tai; Petros Syrris; Nicholas D Carter; Atholl Johnston; Lawrence Goldberg; David W Holt Journal: Transplantation Date: 2002-12-15 Impact factor: 4.939
Authors: S Hoffmeyer; O Burk; O von Richter; H P Arnold; J Brockmöller; A Johne; I Cascorbi; T Gerloff; I Roots; M Eichelbaum; U Brinkmann Journal: Proc Natl Acad Sci U S A Date: 2000-03-28 Impact factor: 11.205