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Population Pharmacokinetic of Monohydroxycarbazepine in epileptic Children

Population Pharmacokinetic of Monohydroxycarbazepine in epil...

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第二十三届全国儿科药学学术年会暨首届中欧儿科临床药学国际论坛和第四届全国儿科药学中青年药师论文报告会

作者： Wang Gang He Cuiyao Wu Qing Liu Bin YuanYonghua LI Yan-mei Huang Zhi Clinical Pharmacy Research Children's Hospital of Chongqing Medical University Ministry of Education Key Laboratory of Child Development and Disorders in Chongqing

Objective:To study the population pharmacokinetic parameters of Oxcarbazepine metabolite monohydroxycarbazepine(MHD) in epileptic ***:We collected the MHD plasma concentration monitoring data of 1370 epileptic children conventional treated with Oxcarbazepine. We followed the thought as the population pharmacokinetic deals with the sparse conventional data and based on Bayesian feedback *** model was set up and population pharmacokinetic parameters of 769 cases of conventional treatment were calculated through NONMEM program The treatment of 601 epileptic children ***:The clearance of MHD was no significantly influenced(P>0.05)by gender,height,Clonazepam(CNP),Nazepam(NP) and Topiramate(TPM);but significantly influenced(Pmodel fitting the pharmacokinetic model of this study The main population pharmacokinetics parameters tβ,V,K,CL of MHD in epileptic children were respectively(8.45±1.47) h,(24.18±5.67) L,(0.084±0.011) *** and(1.976±0.246 ) *** in the monotherapy group;were respectively(6.68±1.18) h,(23.80±5.102) L,(0.106±0.018) *** and(2.46±0.22) *** in the combination *** Clinical follow-up observation,MHD plasma concentration fluctuations,the control rate of epilepsy-like symptoms,the rate of the total efficiency and the adverse reaction incidence of individual treatment group were significantly superior Conclusion:It is necessary to implement or adjust individualized treatment programs using the MHD population pharmacokinetic parameters and it is also necessary for the TDM of the MHD.

关键词： Population pharmacokinetics monohydroxycarbazepine nonlinear mixed effect model children therapeutic drug monitoring(TDM)

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Population pharmacokinetic analysis of norvancomyci

Population pharmacokinetic analysis of norvancomyci

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第十五届国际药理学大会

作者： Zhang Jing Zhang Yingyuan Shi Yaoguo Cao Guoying Yu Jicheng Wu Xiaojie. Institute of Antibiotics Huashan Hospital Fudan University Shanghai 200040 China

＜正＞ Objectives: To investigate the population pharmacokinetics （PPK） of norvan-comycin in different populations of patients and to provide a reliable approach to design a rational regimen in different groups of patients. Methods: NONMEM approach was chosen to establish a PPK model for patients given norvancomycin in this investigation. Results:① Among 146 patients: the mean of the drug clearance （CL） and eliminate half- life （T1/2b） were 0.23 L/h and 154.26 h in 14 patients with severe renal impairment, 2.17 L/h and 22.86 h in 16 patients with moderate renal impairment, and 4.01 L/h and 9.57 h in 45 patients with mild renal impairment, respectively. ② Comparison of 59 elderly patients with non - elderly patients showed 3.94 L/h versus 5.89 L/h for CL, 12.07h versus 6.79 h for T1/2b, and 490.16 mg. h/L versus 283.92 mg. h/L for AUC24. ③ The increased volume of a peripheral distribution as co - administration of norvancomycin with diuretics. Conclusions: The PPK model of norvancomycin was effectively applied to design the regimen for patients with variable renal function..

关键词： norvancomycin PPK nonlinear mixed effect model TDM

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Population pharmacokinetic and pharmacodynamic model of norvancomycin

Population pharmacokinetic and pharmacodynamic model of norv...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： ZHANG Jing~1 ZHANG Yin-yuan~1 SHI Yao-guo~1 RUI Jian-zhong~2 YU Ji-chen~1 CAO Guo-yin~1 WU Ju-fang~1 1 Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai 200040,China 2 Department of Clinical Pharmacology,General Hospital of Nanjing Military Region,Nanjing 210002,Jiangsu,China

AIM:To evaluate the population pharmcokinetics(PPK) and pharmacodynamics(PD)of norvancomycin in patients. METHODS:We enrolled 146 patients who were con- firmed or suspected with gram-positive bacterial infections in this study.A PPK model was developed and validated by the analysis of NONMEM *** PK/PD profiles from the pharmacokinetic parameters in the patients and from MIC values were *** optimal dose regime was calculated by the analyses of the PK/PD model ac- cording to the clinical outcomes and bacterial *** norvancomycin MICs of clinically isolated swains from the patients population were determined by agar dilution meth- ods. RESULTS:The best model was a two compartment phar- macokinetic model with exponential interindividual error and additive residual error statistical *** finding of the study indicated that the change in Ccr values had impacts on drug clearance(CL).For example,CL of pa- tients with decreased renal function would be influenced. The increased volume of a peripheral distribution(V) was observed when norvancomycin was co-administered with *** logistic stepwise analyses revealed that ratio of AUC/MIC is a major factor which could signifi- candy determine the clinical outcomes and bacterial eradi- cation for patients. When the ratio of AUC/MIC was more than 579.90 for Staphylococcus aureus infections or it was more than 637.67 for Enterococal infections,approximately 95% of patients could achieve cure clinical outcome. CONCLUSION:AUC/MIC should be a major PK/ PD parameter to determine efficacy of *** optimized regimen of norvancomycin can be simulated and developed for different subgroups of bacterial infected pa- tients with special physiologic and pathologic features.

关键词： norvancomycin population pharmacokinetics nonlinear mixed effect model pharmacodynamics therapeutic drug monitoring fluorescence polarization immunoassay

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