Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem‐Cell Transplantation

Abstract

Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment.

Population pharmacokinetic modeling and clinical application of vancomycin in Chinese patients hospitalized in intensive care units

“…Kateřina noted that increased Cr levels are a distinct marker for renal dysfunction 24 . In our study, the level of Cr was also negatively correlated with the renal clearance rate of vancomycin, which corresponds with other studies 7,8,25 . Obesity is related to numerous physiological adaptations, which involve increased kidney mass, renal blood flow, creatinine and vancomycin clearance rate 19 .…”

“…As the final model in Table 4 shows, the apparent distribution volume of vancomycin were associated with age and TBW, which is consistent with studies in other patient populations 7,8 . As is well known, the tissue distribution capacity of vancomycin is enhanced in patient populations with greater TBW 31 .…”

“…The population pharmacokinetic (PPK) method is thought to be the most efficient method to improve vancomycin clinical therapeutic effectiveness and perform adverse reaction monitoring by precise dose adjustment 6 . Numerous specific population pharmacokinetic studies of vancomycin have been conducted that well describe the pharmacokinetic characteristics of specific populations of patients, such as those undergoing open heart surgery, extracorporeal membrane oxygenation therapy, high-volume hemofiltration, and critically ill patients et al 7,8 . However, the PPK models for Chinese ICU adult patients are still limited.…”

<p>A Systematic Review of Vancomycin Dosing in Patients with Hematologic Malignancies or Neutropenia</p>

“…Therefore, twenty-one sets of clinical data were finally included. In 18 studies, 17,18,20,[22][23][24][25][26][27][28][29][30][31][34][35][36][37][38] vancomycin was infused intermittently, and 2 studies adopted continuous infusion, 19,21 whereas the remaining 1 conference abstract did not report the specific dosing regimen. 16 For single-arm studies, nine studies included neutropenic hematologic patients consecutively, 16,18,20,21,26,28,31,34,35 while 6 studies included patients with hematologic malignancies without distinguishing neutropenia from non-neutropenia.…”

“…16 For single-arm studies, nine studies included neutropenic hematologic patients consecutively, 16,18,20,21,26,28,31,34,35 while 6 studies included patients with hematologic malignancies without distinguishing neutropenia from non-neutropenia. 17,19,22,27,29,38 Additionally, another two studies included hospitalized patients and took neutropenia as a risk factor. 30,36 Concerning comparative cohort studies, there were two studies comparing neutropenic patients with nonneutropenic patients, 23,25 and another 2 studies focused on the difference between hematologic malignant patients and control groups.…”