title: Population pharmacokinetics of plasma-derived factor IX: procedures for dose individualization.
abstract: BACKGROUND
  Population pharmacokinetic (POPPK) models describing factor IX (FIX) activity levels in plasma, in combination with individual FIX measurements, may be used to individualize dosing in the treatment of hemophilia B.
  
  
  OBJECTIVE
  The aim was to reevaluate a previously developed POPPK model for FIX activity and to explore the number and timing of FIX samples required in pharmacokinetic (PK) dose individualization.
  
  
  METHODS
  The POPPK model was reevaluated using an extended data set. Several sampling schedules, varying with respect to the timing and number of samples, were evaluated in a simulation study with relative dose errors compared between schedules. The performance of individually calculated doses was compared with commonly prescribed FIX doses with respect to the number of patients with a trough FIX activity > 0.01 U mL(-1) .
  
  
  CONCLUSIONS
  A three-compartment PK model best described the FIX activity levels. The number and timing of samples greatly influenced imprecision in dose prediction. Schedules with single samples taken on both day 2 and day 3 were identified as being convenient schedules with an acceptable performance level. Individually calculated doses performed better with respect to patient target attainment than a fixed 40 U kg(-1) dose regardless of how many samples were available to calculate individual doses. The results of this study suggest that PK dose tailoring with limited sampling may be applicable for plasma-derived FIX products.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Brekkan
authors.affiliation: Clinical Coagulation Research Unit, Skåne University Hospital, Malmö, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Berntorp
authors.affiliation: Clinical Coagulation Research Unit, Skåne University Hospital, Malmö, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Jensen
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: E I
authors.initials: EI
authors.lastname: Nielsen
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Jönsson
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D001780:Blood Coagulation Tests; D003029:Coagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D003198:Computer Simulation; D004334:Drug Administration Schedule; D005164:Factor IX / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D015203:Reproducibility of Results; D013997:Time Factors; D055815:Young Adult
chemical_list: D003029:Coagulants; D005164:Factor IX
keywords: Bayesian forecast; coagulation factor IX; hemophilia; patient-specific modeling; pharmacokinetics