title: Characterization of vancomycin pharmacokinetics in the adult acute myeloid leukemia population.
abstract: Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible. Patients hospitalized in the intensive care unit, those with creatinine clearance <30 mL/min or with limb amputation were excluded. Three samples were collected at the following post-infusion time ranges: 1 h, 3-8 h, and 8-24 h post-infusion, contingent on the dosing interval. Pharmacokinetic data were then fit using a Bayesian-based population pharmacokinetic model. A total of 25 acute myeloid leukemia patients were studied with a mean volume in the central compartment (Vc; L/65 kg), volume of distribution at steady state (Vss; L/65 kg) and distributional clearance (CLd; L/h/65 kg) of 15, 38.9, and 9.32, respectively. CLslope was 0.59 (mg of vancomycin clearance per unit of creatinine clearance in mL/min); this value is 21.4% lower than the established literature value (0.75). The derived equation, based upon these values, was reasonably precise at achieving the desired trough concentration using a priori dosing. The mean (CV%) of the achieved trough was 94% (29%) with a range of 66-188%; 3/25 at <75% and >125%]. We have established that the derived dosing equation can place ≈ 75% of adult acute myeloid leukemia patients at vancomycin trough levels within 75-125% of the target trough level.
authors.affiliation: Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Anthony.Jarkowski@roswellpark.org
authors.forename: Anthony
authors.initials: A
authors.lastname: Jarkowski
authors.forename: Alan
authors.initials: A
authors.lastname: Forrest
authors.forename: Richard P
authors.initials: RP
authors.lastname: Sweeney
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Almyroudis
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001499:Bayes Theorem; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000150:complications*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017410:Practice Guidelines as Topic; D011446:Prospective Studies; D013997:Time Factors; D014018:Tissue Distribution; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin