Population pharmacokinetics of vancomycin in Chinese elderly patients and its application for dose individualisation

doi:10.5246/jcps.2020.04.025

Abstract

Abstract:

In the present study, we aimed to develop a population pharmacokinetics (PPK) model of vancomycin (VCM) and proposethe individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findingswere recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance (CL) was significantly influenced by post-craniotomy meningitis (PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.

Key words: Elderly patient, Population pharmacokinetics, Post-craniotomy meningitis, Vancomycin, Dose individualisation

CLC Number:

R943

Supporting:

Jin Zhang, Weiwei Lin, Wei Wu, Xianzhong Guo, Pinfang Huang, Xinhua Lin, Zheng Jiao, Changlian Wang. Population pharmacokinetics of vancomycin in Chinese elderly patients and its application for dose individualisation[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(4): 260-271.

References

[1] Rybak, M.J. The pharmacokinetic and pharmacodynamic properties of vancomycin. Clin. Infect. Dis. 2006, 42, S35-S39.

[2] Rybak, M.; Lomaestro, B.; Rotschafer, J.C.; Moellering, R. Jr, Craig, W.; Billeter, M.; Dalovisio, J.R.; Levine, D.P. 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. Am. J. Health-Syst. Pharm. 2009, 66, 82-98.

[3] Matsumoto, K.; Takesue, Y.; Ohmagari, N.; Mochizuki, T.; Mikamo, H.; Seki, M.; Takakura, S.; Tokimatsu, I.; Takahashi, Y.; Kasahara, K.; Okada, K.; Igarashi, M.; Kobayashi, M.; Hamada, Y.; Kimura, M.; Nishi, Y.; Tanigawara, Y.; Kimura, T. Practice guidelines for therapeutic drug monitoring of vancomycin: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J. Infect. Chemother. 2013, 19, 365-380.

[4] Rodvold, K.A.; Blum, R.A.; Fischer, J.H.; Zokufa, H.Z.; Rotschafer, J.C.; Crossley, K.B.; Riff, L.J. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob. Agents Chemother. 1988, 32, 848-852.

[5] Sánchez, J.L.; Dominguez, A.R.; Lane, J.R.; Anderson, P.O.; Capparelli, E.V.; Cornejo-Bravo, J.M. Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches. Int. J. Clin. Pharmacol. Ther. 2010, 48, 525-533.

[6] Guay, D.R.; Vance-Bryan, K.; Gilliland, S.; Rodvold, K.; Rotschafer, J. Comparison of vancomycin pharmacokinetics in hospitalized elderly and young patients using a Bayesian forecaster. J. Clin. Pharmacol. 1993, 33, 918-922.

[7] Bourguignon, L.; Cazaubon, Y.; Debeurme, G.; Loue, C.; Ducher, M.; Goutelle, S. Pharmacokinetics of vancomycin in elderly patients aged over 80 years. Antimicrob. Agents Chemother. 2016, 60, 4563-4567.

[8] Kim, A.J.; Lee, J.Y.; Choi, S.A.; Shin, W.G. Comparison of the pharmacokinetics of vancomycin in neurosurgical and non-neurosurgical patients. Int. J. Antimicrob. Agents. 2016, 48, 381-387.

[9] Lin Wu, F.L.; Liu, S.S.; Yang, T.Y.; Win, M.F.; Lin, S.W.; Huang, C.F.; Wang, K.C.; Shen, L.J. A larger dose of vancomycin is required in adult neurosurgical intensive care unit patients due to augmented clearance. Ther. Drug Monit. 2015, 37, 609-618.

[10] Lin, W.W.; Wu, W.; Jiao, Z.; Lin, R.F.; Jiang, C.Z.; Huang, P.F.; Liu, Y.W.; Wang, C.L. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens. Eur. J. Clin. Pharmacol. 2016, 72, 29-37.

[11] Da, L.; Hong, S. A study of drug therapy problems in pharmaceutical care. J. Chin. Pharm. Sci. 2009, 18, 354-357.

[12] Thomson, A.H.; Staatz, C.E.; Tobin, C.M.; Gall, M.; Lovering, A.M. Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. J. Antimicrob. Chemother. 2009, 63, 1050-1057.

[13] Kullar, R.; Leonard, S.N.; Davis, S.L.; Delgado, G. Jr, Pogue, J.M.; Wahby, K.A.; Falcione, B.; Rybak, M.J. Validation of the effectiveness of a vancomycin nomogram in achieving target trough concentrations of 15-20 mg/L suggested by the vancomycin consensus guidelines. Pharmacotherapy. 2011, 31, 441-448.

[14] Liu, C.; Bayer, A.; Cosgrove, S.E.; Daum, R.S.; Fridkin, S.K.; Gorwitz, R.J.; Kaplan, S.L.; Karchmer, A.W.; Levine, D.P.; Murray, B.E.; J Rybak, M.; Talan, D.A.; Chambers, H.F. Clinical practice guidelines by the infectious diseases society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: executive summary. Clin. Infect. Dis. 2011, 52, 285-292.

[15] Bautista, J.; Huster, M.; Osterhaus, M. Syva Emit®2000 vancomycin assay. Ther. Drug Monit. 1993, 15, 152.

[16] Levey, A.S.; Stevens, L.A.; Schmid, C.H.; Zhang, Y.L.; Castro, A.F.III, Feldman, H.I.; Kusek, J.W.; Eggers, P.; Van Lente, F.; Greene, T.; Coresh, J.; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 2009, 150, 604-612.

[17] Glatard, A.; Bourguignon, L.; Jelliffe, R.W.; Maire, P.; Neely, M.N.; Goutelle, S. Influence of renal function estimation on pharmacokinetic modeling of vancomycin in elderly patients. Antimicrob. Agents Chemother. 2015, 59, 2986-2994.

[18] Mandema, J.W.; Verotta, D.; Sheiner, L.B. Building population pharmacokinetic: pharmacodynamic models. I. Models for covariate effects. J. Pharmacokinet. Biopharm. 1992, 20, 511-528.

[19] Ette, E.I. Stability and performance of a population pharmacokinetic model. J. Clin. Pharmacol. 1997, 37, 486-495.

[20] Brendel, K.; Comets, E.; Laffont, C.; Laveille, C.; Mentré, F. Metrics for external model evaluation with an application to the population pharmacokinetics of gliclazide. Pharm. Res. 2006, 23, 2036-2049.

[21] Comets, E.; Brendel, K.; Mentré, F. Computing normalised prediction distribution errors to evaluate nonlinear mixed-effect models: the npde add-on package for R. Comput. Methods Programs Biomed. 2008, 90, 154-166.

[22] Lodise, T.P.; Lomaestro, B.; Graves, J.; Drusano, G.L. Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. Antimicrob. Agents Chemother. 2008, 52, 1330-1336.

[23] van der Meer, A.F.; Marcus, M.A.; Touw, D.J.; Proost, J.H.; Neef, C. Optimal sampling strategy development methodology using maximum a posteriori Bayesian estimation. Ther. Drug Monit. 2011, 33, 133-146.

[24] Bondareva, I.B.; Jelliffe, R.W.; Andreeva, O.V.; Bondareva, K.I. Predictability of individualized dosage regimens of carbamazepine and valproate mono- and combination therapy. J. Clin. Pharm. Ther. 2011, 36, 625-636.

[25] He, X.R.; Liu, Z.H.; Ji, S.M.; Liu, T.T.; Li, L.; Zhou, T.Y.; Lu, W. Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in the Chinese people. Acta Pharm. Sin. 2014, 49, 1528-1535.

[26] Scaglione, F.; Paraboni, L. Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: setting appropriate dosing regimens. Int. J. Antimicrob. Agents. 2008, 32, 294-301.

[27] Ott, L.; McClain, C.J.; Gillespie, M.; Young, B. Cytokines and metabolic dysfunction after severe head injury. J. Neurotrauma. 1994, 11, 447-472.

[28] Just, A. Mechanisms of renal blood flow autoregulation: dynamics and contributions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007, 292, R1-R17.

[29] Jennett, B.; Bond, M. Assessment of outcome after severe brain damage. Lancet. 1975, 1, 480-484.

[30] Sadoh, S.; Tsuji, Y.; Tsukamoto, K. Correlation of pharmacokinetic parameters with serum vancomycin concentration in elderly patients with malignancies. Yakugaku Zasshi. 2010, 130, 69-73.

[31] Teramachi, H.; Hatakeyama, H.; Matsushita, R.; Imai, Y.; Miyamoto, K.; Tsuji, A. Evaluation of predictability for vancomycin dosage regimens by the Bayesian method with Japanese population pharmacokinetic parameters. Biol. Pharm. Bull. 2002, 25, 1333-1338.

[32] Purwonugroho, T.A.; Chulavatnatol, S.; Preechagoon, Y.; Chindavijak, B.; Malathum, K.; Bunuparadah, P. Population pharmacokinetics of vancomycin in Thai patients. Sci. World J. 2012, 2012, 762649.

[33] Matsushita, K.; Mahmoodi, B.K.; Woodward, M.; Emberson, J.R.; Jafar, T.H.; Jee, S.H.; Polkinghorne, K.R.; Shankar, A.; Smith, D.H.; Tonelli, M.; Warnock, D.G.; Wen, C.P.; Coresh, J.; Gansevoort, R.T.; Hemmelgarn, B.R.; Levey, A.S.; the Chronic Kidney Disease Prognosis Consortium, F. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 2012, 307, 1941-1951.

[34] David-Neto, E.; Triboni, A.H.; Ramos, F.; Agena, F.; Galante, N.Z.; Altona, M.; Lemos, F.B.; Sapienza, M.T.; Nahas, W.C. Evaluation of MDRD4, CKD-EPI, BIS-1, and modified Cockcroft-Gault equations to estimate glomerular filtration rate in the elderly renal-transplanted recipients. Clin. Transplant. 2016, 30, 1558-1563.

[35] Cartet-Farnier, E.; Goutelle-Audibert, L.; Maire, P.; De la Gastine, B.; Goutelle, S. Implications of using the MDRD or CKD-EPI equation instead of the Cockcroft-Gault equation for estimating renal function and drug dosage adjustment in elderly patients. Fundam. Clin. Pharmacol. 2017, 31, 110-119.

[36] Park, S.Y.; Lee, K.W. Renal assessment using CKD-EPI equation is useful as an early predictor of contrast- induced nephropathy in elderly patients with cancer. J. Geriatr. Oncol. 2017, 8, 44-49.

[37] Staatz, C.E.; Byrne, C.; Thomson, A.H. Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery. Br. J. Clin. Pharmacol. 2006, 61, 164-176.

[38] Tanaka, A.; Aiba, T.; Otsuka, T.; Suemaru, K.; Nishimiya, T.; Inoue, T.; Murase, M.; Kurosaki, Y.; Araki, H. Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function. Antimicrob. Agents Chemother. 2010, 54, 778-782.

[39] Revilla, N.; Martín-Suárez, A.; Pérez, M.P.; González, F.M.; del Mar Fernández de Gatta, M. Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation. Br. J. Clin. Pharmacol. 2010, 70, 201-212.

[40] Chung, J.Y.; Jin, S.J.; Yoon, J.H.; Song, Y.G. Serum cystatin C is a major predictor of vancomycin clearance in a population pharmacokinetic analysis of patients with normal serum creatinine concentrations. J. Korean Med. Sci. 2013, 28, 48-54.

[41] Holford, N.H.; Buclin, T. Safe and effective variability-a criterion for dose individualization. Ther. Drug Monit. 2012, 34, 565-568.