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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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General Research Article

In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring

Author(s): Abigail Ferreira, Helena Martins, José C. Oliveira, Rui Lapa and Nuno Vale*

Volume 22, Issue 2, 2021

Published on: 01 January, 2021

Page: [150 - 162] Pages: 13

DOI: 10.2174/1389200221999210101232417

Price: $65

Abstract

Background: Vancomycin has been in clinical use for nearly 50 years and remains the first-line treatment option for Gram-positive infections, including methicillin-resistant Staphylococcus aureus (MRSA). There are multiple strategies to monitor therapy and adjust the dose of this antibiotic. AUC24/MIC ratio has been demonstrated to be the best parameter to predict the effectiveness and safety of vancomycin, and a target ratio of ≥400 is recommended. Still, trough and peak serum levels at steady-state conditions have been used in clinical settings as an accurate and practical method to monitor vancomycin.

Methods: In this work, we collected and analyzed clinical information of patients being treated in a hospital center in Porto (Portugal) and studied the pharmacokinetics of vancomycin in silico, developing several physiologically based pharmacokinetic (PBPK) models using simulation software GastroPlus™. Different dosages and treatment regimens were studied, and the influence of patients’ age, weight and renal function was evaluated; a simulation population was also performed.

Results: A linear effect of dose and a significant influence of weight and renal function in plasmatic levels of vancomycin was observed.

Conclusion: The results of this work corroborate the accumulation of vancomycin in plasma and identify some parameters that influence the pharmacokinetics of this antibiotic. The importance of therapeutic monitoring of vancomycin is highlighted, and the usefulness of in silico tools, namely PBPK modeling, is demonstrated.

Keywords: Vancomycin, therapeutic drug monitoring, renal function, drug metabolism, PBPK, Gastroplus™.

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[1]
Levine, D.P. Vancomycin: a history. Clin. Infect. Dis., 2006, 42(Supplement_1), S5-S12.
[http://dx.doi.org/10.1086/491709]
[2]
Cataldo, M.A.; Tacconelli, E.; Grilli, E.; Pea, F.; Petrosillo, N. Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis. J. Antimicrob. Chemother., 2012, 67(1), 17-24.
[http://dx.doi.org/10.1093/jac/dkr442] [PMID: 22028203]
[3]
Levine, J.F. Vancomycin: a review. Med. Clin. North Am., 1987, 71(6), 1135-1145.
[http://dx.doi.org/10.1016/S0025-7125(16)30801-X] [PMID: 3320615]
[4]
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(1), 82-98.
[http://dx.doi.org/10.2146/ajhp080434] [PMID: 19106348]
[5]
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. Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin. Infect. Dis., 2011, 52(3), e18-e55.
[http://dx.doi.org/10.1093/cid/ciq146] [PMID: 21208910]
[6]
Marsot, A.; Boulamery, A.; Bruguerolle, B.; Simon, N. Vancomycin: a review of population pharmacokinetic analyses. Clin. Pharmacokinet., 2012, 51(1), 1-13.
[http://dx.doi.org/10.2165/11596390-000000000-00000] [PMID: 22149255]
[7]
Álvarez, R.; López Cortés, L.E.; Molina, J.; Cisneros, J.M.; Pachón, J. Optimizing the clinical use of vancomycin. Antimicrob. Agents Chemother., 2016, 60(5), 2601-2609.
[http://dx.doi.org/10.1128/AAC.03147-14] [PMID: 26856841]
[8]
Bruniera, F.R.; Ferreira, F.M.; Saviolli, L.R.; Bacci, M.R.; Feder, D.; da Luz Gonçalves Pedreira, M.; Sorgini Peterlini, M.A.; Azzalis, L.A.; Campos Junqueira, V.B.; Fonseca, F.L. The use of vancomycin with its therapeutic and adverse effects: a review. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(4), 694-700.
[PMID: 25753888]
[9]
Bamgbola, O. Review of vancomycin-induced renal toxicity: an update. Ther. Adv. Endocrinol. Metab., 2016, 7(3), 136-147.
[http://dx.doi.org/10.1177/2042018816638223] [PMID: 27293542]
[10]
Rybak, M.J. Pharmacodynamics: relation to antimicrobial resistance. Am. J. Infect. Control, 2006, 34(5)(Suppl. 1), S38-S45.
[http://dx.doi.org/10.1016/j.ajic.2006.05.227] [PMID: 16813981]
[11]
Ye, Z.K.; Tang, H.L.; Zhai, S.D. Benefits of therapeutic drug monitoring of vancomycin: a systematic review and meta-analysis. PLoS One, 2013, 8(10), e77169.
[http://dx.doi.org/10.1371/journal.pone.0077169] [PMID: 24204764]
[12]
Avent, M.L.; Vaska, V.L.; Rogers, B.A.; Cheng, A.C.; van Hal, S.J.; Holmes, N.E.; Howden, B.P.; Paterson, D.L. Vancomycin therapeutics and monitoring: a contemporary approach. Intern. Med. J., 2013, 43(2), 110-119.
[http://dx.doi.org/10.1111/imj.12036] [PMID: 23185970]
[13]
Lodise, T.P.; Drusano, G.L.; Zasowski, E.; Dihmess, A.; Lazariu, V.; Cosler, L.; McNutt, L.A. Vancomycin exposure in patients with methicillin-resistant Staphylococcus aureus bloodstream infections: how much is enough? Clin. Infect. Dis., 2014, 59(5), 666-675.
[http://dx.doi.org/10.1093/cid/ciu398] [PMID: 24867791]
[14]
Miller, N.A.; Reddy, M.B.; Heikkinen, A.T.; Lukacova, V.; Parrott, N. Physiologically based pharmacokinetic modelling for first-in-human predictions: an updated model building strategy illustrated with challenging industry case studies. Clin. Pharmacokinet., 2019, 58(6), 727-746.
[http://dx.doi.org/10.1007/s40262-019-00741-9] [PMID: 30729397]
[15]
Wagner, C.; Zhao, P.; Pan, Y.; Hsu, V.; Grillo, J.; Huang, S.M.; Sinha, V. Application of physiologically based pharmacokinetic (PBPK) modeling to support dose selection: report of an FDA public workshop on PBPK. CPT Pharmacometrics Syst. Pharmacol., 2015, 4(4), 226-230.
[http://dx.doi.org/10.1002/psp4.33] [PMID: 26225246]
[16]
Ferreira, A.; Lapa, R.; Vale, N. Combination of gemcitabine with cell-penetrating peptides: a pharmacokinetic approach using in silico tools. Biomolecules, 2019, 9(11), E693.
[http://dx.doi.org/10.3390/biom9110693] [PMID: 31690028]
[17]
Cockcroft, D.W.; Gault, M.H. Prediction of creatinine clearance from serum creatinine. Nephron, 1976, 16(1), 31-41.
[http://dx.doi.org/10.1159/000180580] [PMID: 1244564]

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