Akbar Zunaira, Usman Muhammad, Aamir Muhammad, Saleem Zikria, Khan Muhammad Rehan, Alamri Abdulwahab, Alharbi Mohammed Salem, Osman Gamal Eldin Mohamed
Department of Pharmacy, The University of Lahore, Lahore, Pakistan.
Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore, Pakistan.
PLoS One. 2025 Mar 27;20(3):e0318883. doi: 10.1371/journal.pone.0318883. eCollection 2025.
The pharmacokinetics of voriconazole have been studied across various populations but data specific to the Pakistani cancer population has not yet been reported. The aim of present study was to explore and identify covariates that affect pharmacokinetics of intravenous voriconazole in Pakistani cancer population.
The therapeutic drug monitoring data from January1st, 2023 to December 31st, 2023 of cancer patients receiving intravenous voriconazole for systemic fungal infections were taken from electronic medical record of the hospital. The data were used for the development of population pharmacokinetic model using NONMEM. Impact of various covariates such as age, weight, sex, liver function test, serum creatinine, creatinine clearance, type of cancer (primary diagnosis) and type of fungal infection were assessed through stepwise covariate modeling. Bootstrap analysis and goodness of fit plots were used to evaluate robustness and predictive performance of final model.
One compartment model best described the included data with first order elimination. The value of voriconazole clearance was 6.17 L/h with interindividual variability of 83.7% while volume of distribution was 55.9 L. The clearance of voriconazole was significantly influenced by renal status of patients. Creatinine clearance and primary diagnosis were significant covariates affecting clearance of voriconazole in covariate analysis.
The findings suggest that this model can be used for dosage adjustment based on creatinine clearance and primary diagnosis as they impact significantly on voriconazole clearance in cancer patients. This approach is especially valuable in resource-limited settings like Pakistan, where individualized therapy can enhance the safety and efficacy of antifungal treatment, addressing the unique clinical and demographic challenges in vulnerable populations.
伏立康唑的药代动力学已在不同人群中进行了研究，但尚未有针对巴基斯坦癌症人群的具体数据报道。本研究的目的是探索并确定影响巴基斯坦癌症人群静脉注射伏立康唑药代动力学的协变量。
从医院电子病历中获取2023年1月1日至2023年12月31日接受静脉注射伏立康唑治疗系统性真菌感染的癌症患者的治疗药物监测数据。这些数据用于使用NONMEM开发群体药代动力学模型。通过逐步协变量建模评估各种协变量（如年龄、体重、性别、肝功能检查、血清肌酐、肌酐清除率、癌症类型（初步诊断）和真菌感染类型）的影响。使用自助法分析和拟合优度图来评估最终模型的稳健性和预测性能。
单室模型能最好地描述包含的具有一级消除的数据。伏立康唑清除率为6.17L/h，个体间变异性为83.7%，而分布容积为55.9L。伏立康唑的清除率受患者肾脏状况的显著影响。在协变量分析中，肌酐清除率和初步诊断是影响伏立康唑清除率的显著协变量。
研究结果表明，该模型可用于基于肌酐清除率和初步诊断进行剂量调整，因为它们对癌症患者伏立康唑清除率有显著影响。这种方法在像巴基斯坦这样资源有限的环境中特别有价值，在那里个体化治疗可以提高抗真菌治疗的安全性和有效性，应对弱势群体中独特的临床和人口挑战。
