title: Validation of a limited sampling model to determine etoposide area under the curve.
abstract: OBJECTIVE
  To validate the utility of a previously reported 3-point limited sampling model (LSM) for determining etoposide area under the curve to infinity (AUC(infinity)).
  
  
  METHODS
  Secondary analysis of data from two clinical trials of etoposide.
  
  
  METHODS
  University medical center clinical research center.
  
  
  METHODS
  Thirty-four patients with different malignancies.
  
  
  METHODS
  Etoposide was administered as a 2-hour infusion to 34 patients. Serial plasma samples were drawn over 24 hours after the infusion and analyzed for etoposide by high-performance liquid chromatography.
  
  
  RESULTS
  The 3-point LSM AUC was compared with a 14-point actual AUC calculated by the linear trapezoidal rule. Actual and predicted AUC(infinity) by the LSM were highly correlated (r=0.97, p<0.0001). The LSM predictions had a mean absolute error of 10.9% (95% CI -14.1, -5.3) and a mean error of -9.7% (95% CI 6.9, 14.9). Nine patients with poor AUC(infinity) estimations by the LSM (error > 12%) tended to have abnormally low or high peak concentrations.
  
  
  CONCLUSIONS
  Our findings suggest the development of more robust LSM using other techniques, such as pharmacostatistical models, that can accommodate a greater degree of pharmacokinetic variability.
authors.affiliation: Division of Oncology and Clinical Pharmacology, Stanford University School of Medicine, California 94037, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Lum
authors.forename: K J
authors.initials: KJ
authors.lastname: Lane
authors.forename: T W
authors.initials: TW
authors.lastname: Synold
authors.forename: A
authors.initials: A
authors.lastname: Goram
authors.forename: S B
authors.initials: SB
authors.lastname: Charnick
authors.forename: B I
authors.initials: BI
authors.lastname: Sikic
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005047:Etoposide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D012494:Sampling Studies
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide