Augmented Renal Clearance of Vancomycin in Hematologic Malignancy Patients

Abstract

The pharmacokinetics of vancomycin (VAN) was retrospectively examined based on trough concentrations at large scale to identify pharmacokinetic differences between Japanese hematologic malignancy and non-malignancy patients. Data from 261 hematologic malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN estimated by an empirical Bayesian method, were collected and analyzed. Our results showed significantly higher values for VAN clearance and shorter elimination half-lives in patients with hematologic malignancies than non-malignancy patients. In addition, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clearance significantly increased in relation to hematologic malignancies. In conclusion, since in hematologic cancer patients VAN clearance is increased, the blood concentration of VAN becomes lower than expected and this may contribute to the survival of resistant bacteria when VAN is administered at low doses. These results suggest that early monitoring of VAN levels in hematologic cancer patients might be recommended to maintain desired effects without side-effects.

Vancomycin population pharmacokinetics and dosing recommendations in haematologic malignancy with augmented renal clearance children

“…This issue has gained increasing attention. Previous studies have shown that there is a significant correlation between haematologic malignancy and ARC expression, and haematologic malignancy is highly likely to develop into ARC 7,11 . There have been vancomycin haematologic malignancy PPK studies 9,10,12 and ARC PPK studies 13‐15 .…”

Increased Vancomycin Clearance in Patients with Solid Malignancies

“…Previously, we compared VAN pharmacokinetic parameters of non-malignancy patients and hematological malignancy patients by multiple regression analysis using propensity score matching, and found that CL VAN is effected by hematological malignancy. 23) Therefore, we concluded that the presence of malignant tumor was one factors affecting CL VAN , regardless of hematological malignancy or solid malignant tumor. A partial regression of each stage obtained by adjusting the patient background using the propensity score matching method for patients with solid malignant tumors is generally considered to be clinically significant, since the average value of CL VAN of non-malignancy patients is approximately 0.05 L/hr/kg.…”

“…A population pharmacokinetic parameter set for Japanese adult patients 26) was adopted as described previously. 23)…”

“…Previously, we have reported that hematological malignancy was a factor affecting CL VAN based on the results obtained by comparing VAN pharmacokinetic parameters in non-malignancy patients with hematological malignancy patients by means of multiple regression analysis using propensity score matchings. 23) Unfortunately, for Japanese patients with solid malignancies, there are few large scale studies on VAN that provide pharmacokinetic parameters, such as CL VAN and in small scale studies, confounding factors are not considered. 22) In solid malignancies, the degree of confounding factors varies according to the stage.…”

A simple scoring method to predict augmented renal clearance in haematologic malignancies

“…Although it is important to evaluate the risk for ARC in these patients before starting the treatment and to design the antibiotic administration appropriately, there is no report for ARC in patients with malignancy. However, some animal and human studies have reported increased clearance of VCM in malignancies 13,14 . We hypothesized that ARC is a common phenomenon in patients with haematopoietic malignancies, as well as in critically ill patients.…”