title: Population pharmacokinetics: development of a medical intensive care unit-specific gentamicin dosing nomogram.
abstract: OBJECTIVE
  This study was designed to develop a population-specific dosing nomogram for gentamicin in medical intensive care unit (MICU) patients using the population pharmacokinetic program nonparametric expectation maximization (NPEM).
  
  
  METHODS
  Observational clinical gentamicin dosing data were collected, entered into the USC*PACK database program PASTRX, and downloaded into the population pharmacokinetic program NPEM. NPEM generated population pharmacokinetic parameter values that were used to develop a gentamicin dosing nomogram. The nomogram was tested in the next 15 patients admitted to MICU to determine accuracy. Doses given per the MICU and the Hull-Sarubbi nomograms were compared with doses based on actual patient-specific pharmacokinetic parameter values. Reliability coefficients (intraclass correlation coefficients) were calculated to assess the agreement between observations.
  
  
  METHODS
  Data were gathered from patients receiving gentamicin therapy in the MICU, Presbyterian University Hospital, Pittsburgh.
  
  
  METHODS
  Baseline population pharmacokinetic parameter values were determined in 36 MICU patients receiving gentamicin therapy. Patients with renal failure receiving hemodialysis or another mechanical method of blood clearance or fluid removal were excluded. The population parameter values in the form of a dosing nomogram were then used prospectively to dose gentamicin in 15 patients.
  
  
  RESULTS
  NPEM generated population parameter values similar to those previously published using the Sawchuk-Zaske method in ICU patients. The mean volume of distribution generated using NPEM was 0.34 +/- 0.12 L/kg. The relationship between creatinine clearance (Clcr) and elimination rate constant (Ke) was: Ke = 0.00218 x Clcr + 0.007. The nomogram-derived doses correlated with doses determined by using actual patient-specific pharmacokinetic values (p < 0.05). The Hull-Sarubbi derived doses, however, did not correlate with patient-specific doses (p > 0.05). Only one patient had a peak concentration < 6 mg/L. Two of 15 patients had trough concentrations prior to the first maintenance dose > 2 mg/L.
  
  
  CONCLUSIONS
  The use of NPEM to generate population-specific pharmacokinetic parameter values has been previously described. Application of population-specific dosing nomograms can improve initial dosing regimens such that conventional therapeutic concentrations can be achieved early in therapy. This nomogram, however, does not preclude follow-up patient-specific pharmacokinetic analysis.
authors.affiliation: Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, PA.
authors.forename: S M
authors.initials: SM
authors.lastname: Watling
authors.forename: D F
authors.initials: DF
authors.lastname: Kisor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism; D006785:Hospitals, University; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D005839:Gentamicins