title: Effect of diltiazem on the pharmacokinetics of microemulsion cyclosporine A in renal transplantation.
abstract: OBJECTIVE
  Diltiazem might be used as a cyclosporine A (CsA)-sparing agent. There is evidence that CsA (C2) level is the best single point blood sampling for monitoring the CsA level. The authors, therefore, studied the effect of diltiazem on the pharmacokinetics (PK) of CsA, including C2, in renal transplant patients.
  
  
  METHODS
  Twenty-five CsA-treated renal transplant patients, with neither diseases nor agents that alter the PK of CsA, were enrolled in the present study. The PK of CsA was studied in all patients before and 2 weeks after taking diltiazem.
  
  
  RESULTS
  The area under the concentration-time curve (AUC) of CsA was obtained by 2 methods, AUC0-4 and AUC0-12. Before taking diltiazem, the correlation (r) between C0 with AUC0-4 and C0 with AUC0-12 were 0.799 and 0.871, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.956, respectively (p = 0.01). Time to maximum concentration (Tmax) of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. After two weeks of taking diltiazem, r between C0 with AUC0-4 and C0 with AUC0-12 were 0.577 and 0.784, respectively (p = 0.01), r between C2 with AUC0-4 and C2 with AUC0-12 were 0.988 and 0.896, respectively (p = 0.01). Tmax of CsA was at 1.5 hr (1.5-4.0 hr) [median (range)]. The dosage of CsA could be reduced by 25.8% to maintain the same levels of C0 and C2 in the same patients after taking diltiazem.
  
  
  CONCLUSIONS
  Diltiazem slightly altered the correlation between C2 with AUC of CsA. This indicates that C2 is the best single point blood sampling to monitor the therapeutic levels of CsA in renal transplant patients who are taking diltiazem.
authors.affiliation: Renal Division, Department of Medicine, Rajavithi Hospital.
authors.forename: Sakarn
authors.initials: S
authors.lastname: Bunnag
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Vareesangthip
authors.forename: Leena
authors.initials: L
authors.lastname: Ong-ajyooth
mesh_terms: D000042:Absorption; D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004655:Emulsions; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D011184:Postoperative Period; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D014665:Vasodilator Agents; D016572:Cyclosporine; D004110:Diltiazem