title: Population pharmacokinetics of teicoplanin and attainment of pharmacokinetic/pharmacodynamic targets in adult patients with haematological malignancy.
abstract: OBJECTIVE
  To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations.
  
  
  METHODS
  This was a hospital-based clinical trial (EudraCT 2013-004535-72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics.
  
  
  RESULTS
  Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC48-72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC48-72hand trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours.
  
  
  CONCLUSIONS
  To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland.
authors.forename: C J
authors.initials: CJ
authors.lastname: Byrne
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Centre for Translational Anti-Infective Pharmacodynamics, The University of Queensland, Brisbane, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Pathology Queensland, Brisbane, Australia.
authors.forename: B
authors.initials: B
authors.lastname: McWhinney
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland.
authors.forename: S A
authors.initials: SA
authors.lastname: Ryder
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: J P
authors.initials: JP
authors.lastname: Fennell
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: O'Byrne
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Deasy
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Egan
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Desmond
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: H
authors.initials: H
authors.lastname: Enright
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Ireland. Electronic address: ddarcy@tcd.ie.
authors.forename: D M
authors.initials: DM
authors.lastname: D'Arcy
authors.affiliation: Tallaght Hospital, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: McHugh
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017334:Teicoplanin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin
keywords: Glycopeptides; Haematological malignancy; Monte Carlo simulations; Population pharmacokinetics; Teicoplanin; Therapeutic drug monitoring