Wei-Wei Lin1, Wei Wu1, Zheng Jiao2, Rong-Fang Lin1, Chang-Zhen Jiang3, Pin-Fang Huang1, Yi-Wei Liu1, Chang-Lian Wang4. 1. Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, 20 Cha Zhong M. Rd, Taijiang, Fuzhou, 350005, People's Republic of China. 2. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Wu Lu Mu Qi M. Rd, Shanghai, 20040, People's Republic of China. zjiao@fudan.edu.cn. 3. Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, 20 Cha Zhong M. Rd, Taijiang, Fuzhou, 350005, People's Republic of China. 4. Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, 20 Cha Zhong M. Rd, Taijiang, Fuzhou, 350005, People's Republic of China. WCL@medmail.com.cn.
Abstract
PURPOSE: Vancomycin (VCM) is a first-line antibacterial drug used to treat post-craniotomy meningitis (PCM). VCM pharmacokinetic parameters are altered in PCM patients, compared to those in other patients. Although VCM population pharmacokinetics (PPK) has been reported, changes in VCM PPK in adult Chinese PCM patients remain unknown. We developed a VCM PPK model in adult Chinese PCM patients and proposed a new strategy for individualising VCM administration using this model. METHODS: Data was obtained from a prospective study of 100 adult PCM patients in the Neurosurgery Department of the First Affiliated Hospital of Fujian Medical University. The trough concentrations at steady state were determined by enzyme multiplied immunoassay. Nonlinear mixed-effect model software was employed to develop the PPK model. The final model was evaluated using the bootstrap method and normalised prediction error distribution and through the testing of 20 independent adult PCM patients. RESULTS: VCM clearance in PCM patients was higher than that observed in other patients. Creatinine clearance affected VCM clearance, whereas no co-administered drugs influenced VCM pharmacokinetics. Trough concentrations were accurately predicted by the final model, while the prediction errors were less than ±32 %. Moreover, a new strategy for individualising VCM regimens using the PPK model was proposed and validated. CONCLUSIONS: A PPK model was developed to estimate the individual clearance in inpatients receiving intravenously infused VCM and could be used to develop individualised dosing of adult Chinese PCM patients.
PURPOSE:Vancomycin (VCM) is a first-line antibacterial drug used to treat post-craniotomy meningitis (PCM). VCM pharmacokinetic parameters are altered in PCM patients, compared to those in other patients. Although VCM population pharmacokinetics (PPK) has been reported, changes in VCM PPK in adult Chinese PCM patients remain unknown. We developed a VCM PPK model in adult Chinese PCM patients and proposed a new strategy for individualising VCM administration using this model. METHODS: Data was obtained from a prospective study of 100 adult PCM patients in the Neurosurgery Department of the First Affiliated Hospital of Fujian Medical University. The trough concentrations at steady state were determined by enzyme multiplied immunoassay. Nonlinear mixed-effect model software was employed to develop the PPK model. The final model was evaluated using the bootstrap method and normalised prediction error distribution and through the testing of 20 independent adult PCM patients. RESULTS:VCM clearance in PCM patients was higher than that observed in other patients. Creatinine clearance affected VCM clearance, whereas no co-administered drugs influenced VCM pharmacokinetics. Trough concentrations were accurately predicted by the final model, while the prediction errors were less than ±32 %. Moreover, a new strategy for individualising VCM regimens using the PPK model was proposed and validated. CONCLUSIONS: A PPK model was developed to estimate the individual clearance in inpatients receiving intravenously infused VCM and could be used to develop individualised dosing of adult Chinese PCM patients.
Entities:
Keywords:
Adult Chinese patients; Dose individualisation; Population pharmacokinetics; Post-craniotomy meningitis; Vancomycin
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