title: A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period.
abstract: BACKGROUND
  Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center.
  
  
  METHODS
  A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d).
  
  
  RESULTS
  The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1, *1/*3, and *3/*3, respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r(2) = 0.307) and the stable dose at months 1 to 3 (r(2) = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r(2) = 0.546) and the stable dose at months 1 to 3 (r(2) = 0.406).
  
  
  CONCLUSIONS
  There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Electronic address: ntownamchai@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Townamchai
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: W
authors.initials: W
authors.lastname: Chancharoenthana
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Vadcharavivad
authors.affiliation: Pharmacokinetic Research Unit, Department of Pharmacology, Chulalongkorn University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Chariyavilaskul
authors.affiliation: Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.
authors.forename: K
authors.initials: K
authors.lastname: Pongpirul
authors.affiliation: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: A
authors.initials: A
authors.lastname: Leelahavanichkul
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: S
authors.initials: S
authors.lastname: Watanatorn
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: Y
authors.initials: Y
authors.lastname: Avihingsanon
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Praditpornsilpa
authors.affiliation: Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
authors.forename: N
authors.initials: N
authors.lastname: Srisawat
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus