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.

Pharmacokinetics of vancomycin in patients with different renal function levels

“…The vancomycin particle has a molecular weight of 1,450 and has structural chemical groups for essential conjugation with other compounds [ 25 ]. Some authors have reported measurable vancomycin concentrations in the bile after intravenous administration of vancomycin, which also supports the possibility of an extrarenal path for vancomycin elimination [ 26 ].…”

“…In some earlier pharmacokinetic studies, it was suggested that patients with malignancy had increased clearance of vancomycin [ 25 ]. Conversely, other authors reported that patients with acute myeloid leukemia had lower clearance of vancomycin [ 26 ]. It was also noted that body weight may affect clearance of vancomycin, as an increase in weight was related to higher values of both clearance and volume of distribution [ 27 , 28 ].…”

Predictive performance of Vancomycin population pharmacokinetic models in Iranian patients underwent hematopoietic stem cell transplantation

“…[ 3 ] Determination of an optimal initial vancomycin dosing-regimen is crucial to reach recommended serum concentrations as quickly as possible because it could results in better bacterial eradication and improved outcome. [ 4 ] The observed intra and inter-patient variability in vancomycin pharmacokinetics led to the integration of vancomycin therapeutic drug monitoring and pharmacokinetic approaches into standard practice. [ 4 5 6 ] Hence, without considering vancomycin pharmacokinetic characteristics in this specific population of patients, initial empirical vancomycin treatment may not be optimal.…”

“…[ 4 ] The observed intra and inter-patient variability in vancomycin pharmacokinetics led to the integration of vancomycin therapeutic drug monitoring and pharmacokinetic approaches into standard practice. [ 4 5 6 ] Hence, without considering vancomycin pharmacokinetic characteristics in this specific population of patients, initial empirical vancomycin treatment may not be optimal.…”

“…Studies in patients with hematologic malignancies and neutropenic fever revealed different vancomycin pharmacokinetic parameters from other patients’ populations. [ 4 13 14 15 ] Little is known about vancomycin pharmacokinetics in HSCT patients. A recent study showed 70–80% higher mean vancomycin clearance (CL) in HSCT patients than what had been observed in adult medical and surgical patients.…”