title: Dosing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients.
abstract: BACKGROUND
  Starting doses of tacrolimus and ciclosporin are typically chosen on a calculated mg/kg bodyweight basis. After initiation of treatment, doses are adjusted with therapeutic drug monitoring (TDM). This trial-and-error approach has been accepted by most physicians and pharmacists involved in the care of transplanted patients.
  
  
  METHODS
  Dosing algorithms have only fairly recently been proposed to better individualize the starting dose. This review provides an overview of all the currently available dosing algorithms in adult and children for the starting dose of ciclosporin, tacrolimus and mycophenolic acid. In these algorithms, multiple other covariates influencing the starting dose, such as age, hematocrit, comedication and genotype are taken into account. After selecting the starting dose with an algorithm and after initiation of treatment, TDM will, however, remain necessary. Whether or not implementation of such algorithms will improve clinical outcome remains to be demonstrated.
  
  
  CONCLUSIONS
  First of all an algorithm needs to be validated, against an independent dataset. Second, in a prospective study the algorithm should prove to reduce the time to reach the target concentration, and to reduce the number of patients with drug concentrations (far) outside the therapeutic window. Finally, a clinical trial demonstrating a benefit on clinical outcome will be crucial in achieving broad acceptance of calculating starting dose using individualized dosing algorithms.
authors: Erasmus MC, University Medical Center Rotterdam, Department of Hospital Pharmacy , Room Na-206, P.O. Box 2040, 3000 CA, Rotterdam , The Netherlands +31 10 703 3202 ; +31 10 703 2400 ; l.andrews@erasmusmc.nl.
authors: Louise M
authors: LM
authors: Andrews
authors: Natalia
authors: N
authors: Riva
authors: Brenda C
authors: BC
authors: de Winter
authors: Dennis A
authors: DA
authors: Hesselink
authors: Saskia N
authors: SN
authors: de Wildt
authors: Karlien
authors: K
authors: Cransberg
authors: Teun
authors: T
authors: van Gelder
mesh_terms: D000328:Adult; D000465:Algorithms; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D016377:Organ Transplantation / Q000379:methods*; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: algorithm; ciclosporin; dose; equation; immunosuppressive drugs; kidney; liver; mycophenolic acid; pharmacokinetics; tacrolimus; therapeutic drug monitoring; transplantation