title: Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome.
abstract: BACKGROUND
  Tacrolimus has gained acceptance in the management of steroid-resistant nephrotic syndrome (SRNS) in children. Due to limited data, therapeutic range is extrapolated from pediatric renal transplant recipients. This study was designed to assess therapeutic efficacy of tacrolimus in children with SRNS and its correlation with inter-dose area under concentration curve (AUC0-12 h) and trough concentration (C0).
  
  
  METHODS
  Pre dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4, 8, and 12 h after drug administration blood samples were collected in 25 children who were on tacrolimus for a minimum of 3 months and AUC0-12 h was calculated.
  
  
  RESULTS
  There was an 80% (20/25) response rate with 64% (16/25) children achieving complete remission. Median C0 in remission was higher than in relapse group (2.95 ng/ml, versus 1.20 ng/ml, p = 0.005). Median AUC0-12 h in remission was higher compared to those in relapse group (79.75 versus 35.15 μg × h/l; p = 0.025). Maximum concentration after drug administration (Cmax) among the groups was not significantly different. There was a significant correlation between C0 and AUC0-12 h (r = 0.79); and Cmax and AUC0-12 h (r = 0.84). Five patients had a rise in serum creatinine, of which four were still proteinuric and had lower C0 and AUC0-12 h. No other adverse effect was noted.
  
  
  CONCLUSIONS
  Tacrolimus had beneficial clinical response in SRNS. Target C0 and AUC0-12 h level for treatment remission was higher than those in relapse in children with SRNS but was lower than required in transplant recipient.
authors.affiliation: Paediatric Nephrology Unit, Department of Paediatrics, Christian Medical College, Vellore, Tamilnadu, India. dr.afsanajahan@gmail.com.
authors.forename: Afsana
authors.initials: A
authors.lastname: Jahan
authors.affiliation: Department of Clinical Pharmacology, Christian Medical College, Vellore, Tamilnadu, India.
authors.forename: Ratna
authors.initials: R
authors.lastname: Prabha
authors.affiliation: Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
authors.forename: Swasti
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Department of Clinical Pharmacology, Christian Medical College, Vellore, Tamilnadu, India.
authors.forename: Binu
authors.initials: B
authors.lastname: Mathew
authors.affiliation: Department of Clinical Pharmacology, Christian Medical College, Vellore, Tamilnadu, India.
authors.forename: Denise
authors.initials: D
authors.lastname: Fleming
authors.affiliation: Paediatric Nephrology Unit, Department of Paediatrics, Christian Medical College, Vellore, Tamilnadu, India.
authors.forename: Indira
authors.initials: I
authors.lastname: Agarwal
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy*; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Nephrotic syndrome; Pharmacokinetics; Tacrolimus