Population Pharmacokinetics of Vancomycin in Chinese Neonates
LI Jing-jing1, LIU Yi-xi2,3, TANG Lian1, WENG Xiao-hong1, WANG San-nan4, JIAO Zheng2*, SHANG Er-ning1*
1. Department of Pharmacy, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou 215002, China; 2. Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai 200040, China; 3. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China; 4. Department of Neonatology, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou 215002, China
Abstract��OBJECTIVE To investigate the population pharmacokinetics of vancomycin (VAN) in Chinese neonates by nonlinear mixes-effects modeling software (NONMEM). METHODS One hundred and fifty-four VAN serum trough data from 91 neonatal patients were retrospectively collected from Suzhou Hospital Affiliated to Nanjing Medical University. A one-compartment model with first order elimination was used to describe structure pharmacokinetic model, and physiological maturity model was employed to screen covariates. The stability and prediction of the final model were evaluated by Bootstrap and normalized prediction distribution error (NPDE). The final model was applied to evaluate the percentage of AUC0-24 h/MIC �� 400 in neonatal patients by Monte Carlo Simulation, who were stratified according to gestational weeks, age and serum creatinine. RESULTS The weight, postmenstrual age and serum creatinine were identified as the most significant covariate on clearance. Bootstrap and NPDE showed the satisfactory stability and prediction performance of the final model. Moreover, the final model indicated that 96% of neonates with low serum creatinine (15 ��mol��L-1) were not getting AUC0-24 h/MIC��400, according to the current guidelines. CONCLUSION The population pharmacokinetic model of vancomycin in neonates is established successfully and could provide basis for the individualized therapy in neonatal patients.
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LI Jing-jing, LIU Yi-xi, TANG Lian, WENG Xiao-hong, WANG San-nan, JIAO Zheng, SHANG Er-ning. Population Pharmacokinetics of Vancomycin in Chinese Neonates. Chinese Pharmaceutical Journal, 2017, 52(16): 1434-1441.
LIU C, BAYER A, COSGROVE S E, et al. Clinical practice guideline by the Infection Disease Society of America for the treatment of methicillin-resistaont Staphylococcus aureus infections in adult and children[J]. Clin Infect Dis, 2011, 52(3):18-55.
[2]
RYBAK M, LOMAESTRO B, ROTSCHAFER J C, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists[J]. Am J Health Syst Pharm, 2009, 66(1): 82-98.
[3]
HUANG Z Y, XIAO Y H, ZHANG J, et al. A consensus of clinical application of vancomycin by Chinese expert group of vancomycin[J]. Chin J New Drugs Clin Rem (�й���ҩ���ٴ���־), 2011, 30(8): 561-573.
[4]
LI J J, TANG L, WANG S N, et al. Evaluation of clinical necessity of establishing a population pharmacokinetic model of vancomycin in neonates[J]. Chin Hosp Pharm J (�й�ҽԺҩѧ��־), 2015, 35(22): 2034-2037.
[5]
TANG L, WANG S N, LI J J, et al. Serum drug concentration monitoring of vancomycin in the treatment of neonatal bacterical sepsis and clinical effect analysis[J]. Pharm Care Res (ҩѧ�������о�), 2016, 16(1): 25-28.
[6]
YEH Y C, YEH K M, LIN T Y, et al. Impact of vancomycin MIC creep on patients with methicillin-resistant Staphylococcus aureus bacteremia[J]. J Microbiol Immunol Infect, 2012,45(3):214-220.
[7]
LO Y L, VAN HASSELT J G, HENG S C, et al. Population pharmacokinetics of vancomycin in premature malaysian neonates: identification of predictors for dosing determination[J]. Antimicrob Agents Chemother, 2010, 54(6): 2626-2632.
[8]
KIMURA T, SUNAKAWA K, MATSUURA N, et al. Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates[J]. Antimicrob Agents Chemother, 2004, 48(4): 1159-1167.
[9]
ZHAO W, LOPEZ E, BIRAN V, et al. Vancomycin continuous infusion in neonates: dosing optimisation and therapeutic drug monitoring[J]. Arch Dis Child, 2013, 98(6): 449-453.
[10]
OUDIN C, VIALET R, BOULAMERY A, et al. Vancomycin prescription in neonates and young infants: toward a simplified dosage[J]. Arch Dis Child Fetal Neonatal Ed, 2011, 96(5):365-370.
[11]
GRIMSLEY C, AH T. Pharmacokinetics and dose requirements of vancomycin in neonates[J]. Arch Dis Child Fetal Neonatal Ed, 1999, 81(3): 221-227.
[12]
MULLA H, POOBONI S. Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation[J]. Br J Clin Pharmacol, 2005, 60(3): 265-275.
[13]
ANDERSON B J, ALLEGAERT K, VAN DEN ANKER J N, et al. Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance[J]. Br J Clin Pharmacol, 2007, 63(1): 75-84.
[14]
MARQU��S-MI�PANA M R, SAADEDDIN A, JE P. Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline[J]. Br J Pharmacol, 2010, 70(5): 713-720.
[15]
SEAY R E, BRUNDAGE R C, JENSEN P D, et al. Population pharmacokinetics of vancomycin in neonates[J]. Clin Pharmacol Ther, 1994, 56(2): 169-175.
[16]
DE HOOG M, SCHOEMAKER R C, MOUTON J W, et al. Vancomycin population pharmacokinetics in neonates[J]. Clin Pharmacol Ther, 2000, 67(4): 360-367.
[17]
MEHROTRA N, TANG L, PHELPS S J, et al. Evaluation of vancomycin dosing regimens in preterm and term neonates using Monte Carlo simulations[J]. Pharmacotherapy, 2012, 32(5): 408-419.
[18]
HE X R, LIU Z H, JI S M, et al. Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in the Chinese people[J]. Acta Pharm Sin (ҩѧѧ��), 2014, 49(11): 1528-1535.
[19]
LIU Y O, CHEN C Y, SHENG X Y, et al. Validation of vancomycin population pharmacokinetic model for pediatric patients[J]. Chin Pharm J(�й�ҩѧ��־), 2016, 51(14): 1245-1251.
[20]
DENG C, LIU T, ZHOU T, et al. Initial dosage regimens of vancomycin for Chinese adult patients based on PPK analysis[J]. Int J Clin Pharm Ther, 2013, 51(5): 407-415.
[21]
SCHWARTZ G J, BRION L P, SPITZER A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents[J]. Pediatr Clin North Am, 1987, 34(3): 571-590.
[22]
TOD M, JULLIEN V, PONS G. Facilitation of drug evaluation in children by population methods and modeling[J]. Clin Pharmacokinet, 2008, 47(4): 231-243.
[23]
JACQZ-AIGRAIN E, LEROUX S, ZHAO W, et al. How to use vancomycin optimally in neonates remaining questions[J]. Expert Rev Clin Pharmacol, 2015, 8(5): 635-648.
[24]
ANDERSON B J, HOLFORD N H. Mechanism-based concepts of size and maturity in pharmacokinetics[J]. Annu Rev Pharmacol Toxicol, 2008, 48(1): 303-332.
[25]
ALLEGAERT K, ANDERSON B J, VAN D, et al. Renal drug clearance in preterm neonates: relation to prenatal growth[J]. Ther Drug Monit, 2007, 29(3): 284-291.
[26]
WU W. Study on population pharmacokinetic and individualized administration of vancomycin[D]. Fuzhou: Fujian Medical University, 2013.
[27]
LING J, QIAN L X, DING J J, et al. Effects of multiple-trough sampling design and algorithm on the estimation of population and individual pharmacokinetic parameters[J]. Acta Pharm Sin (ҩѧѧ��), 2014, 49(5): 686-694.
2017, Vol. 52 
