BACKGROUND Gram-positive bacterial infections are considered one of the major causes of mortality and morbidity in patients with cancer. Hence, the challenge lies in regulating the pervasive use of vancomycin in the management of infections facing such patients due to the anomalous vancomycin pharmacokinetics (PKs) and pharmacodynamics (PDs). Inappropriate vancomycin exposure is associated with toxicity, pathogen resistance, and therapeutic failure. OBJECTIVE The aim of this study was to estimate vancomycin PK in patients with cancer and without cancer. The standard dosage regimens of vancomycin were then evaluated using data from PK modeling. METHODS In this observational PK study, the data were extracted from a matched patient cohort of those with cancer and those without cancer. Pharmacokinetic analysis was performed using Monolix version 4.4, and the PK parameters were compared in both groups (cancer vs noncancer). The standard and suggested vancomycin dosing regimens were evaluated using PK/PD modeling and Monte Carlo Simulations. RESULTS In total, 448 blood samples were analyzed from 147 patients enrolled in this study, of which 73 patients had cancer and 74 patients were noncancer patients. In general, no significant differences were observed between the two groups (cancer vs noncancer) in all characteristics except for the vancomycin levels, which were significantly lower in patients with cancer (p = 0.00104). This analysis showed that patients with cancer showed a significantly higher vancomycin clearance than noncancer patients (p = 0.002), whereas the volume of distribution (V) was found to be similar in both groups (p = 0.83).This resulted in most of the patients failing to achieve the target area under the curve from zero to 24 hours (AUC 0-2) to the minimum inhibitory concentration. These data showed that a higher maintenance dose of vancomycin is required to achieve the PD target. CONCLUSIONS The findings of this study showed that the patients with cancer have lower levels of vancomycin due to higher clearance than noncancer patients. Thus, higher doses than the standard vancomycin doses may be needed to treat invasive Methicillin-resistant Staphylococcus aureus infections in patients with cancer.

Lithium is an effective agent approved for the treatment of bipolar disorder. It has narrow therapeutic window and significant variability in its pharmacokinetic. The aim of this study is to determine the population pharmacokinetics of lithium in patients with bipolar disorder in Saudi Arabia and to identify the factors that explain variability. A retrospective chart review was performed on patients with bipolar disorder who received oral lithium. The population pharmacokinetic models were developed using Monolix 4.4. After the appropriate base model was established, five covariates were tested, namely age, sex, weight, serum creatinine, and creatinine clearance. The analysis included a total of 170 lithium plasma concentrations from 31 patients. The data were adequately described by a two-compartment open model with linear absorption and elimination. The average parameter estimates for lithium CL/F, V1/F, V2/F, and Q/F were estimated. The inter-individual variability (coefficients of variation) in CL was 42%. The most significant covariate on lithium CL was found to be creatinine clearance. The population pharmacokinetic model of lithium in patients with bipolar disorder in Saudi Arabia was established. Our findings showed that creatinine clearance is the most significant covariate on lithium clearance. Further studies are required to understand the factors that may influence the pharmacokinetics of lithium and assist in drug dosage decisions.