The dose regimen formulation of doxycycline hydrochloride and florfenicol injection based on ex vivo pharmacokinetic-pharmacodynamic modeling against the Actinobacillus pleuropneumoniae in pigs

Springer Science and Business Media LLC - Tập 3 - Trang 1-13 - 2023
Yuanyuan Yuan1,2,3, Boyu An1,3, Shuyu Xie1,3, Wei Qu1,3, Haihong Hao1,3, Lingli Huang1,3, Wanhe Luo1, Jixiang Liang1, Dapeng Peng1,2,3,4,5
1National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China
2State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, People’s Republic of China
3College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, People’s Republic of China
4Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan, People’s Republic of China
5Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, People’s Republic of China

Tóm tắt

Doxycycline hydrochloride and florfenicol combination (DoxHcl&FF) is an effective treatment for respiratory diseases. In the study, our objective was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae (APP) in porcine pulmonary epithelial lining fluid (PELF) and the optimal dosage scheme to avoid the development of resistance. The DoxHcl&FF was administered intramuscularly (IM) at 20 mg/kg, and the PELF was collected at different time points. The minimum inhibitory concentration (MIC) and time-mortality curves were also included in the study. Based on the sigmoid Emax equation and dose equations, the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve (AUC0-24h)/MIC values in PELF and achieve bacteriostatic activity, bactericidal activity and the virtual eradication of bacteria. The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters. The peak concentration (Cmax) of FF in healthy and diseased pigs was 8.87 ± 0.08 μg/mL and 8.67 ± 0.07 μg/mL, the AUC0-24h were 172.75 ± 2.52 h·μg/mL and 180.22 ± 3.13 h·μg/mL, the Cmax of DoxHcl was 7.91 ± 0.09 μg/mL and 7.99 ± 0.05 μg/mL, and the AUC0-24h was 129.96 ± 3.70 h·μg/mL and 169.82 ± 4.38 h·μg/mL. DoxHcl&FF showed strong concentration-dependent tendencies. The bacteriostatic, bactericidal, and elimination activity were calculated as 5.61, 18.83 and 32.68 h, and the doses were 1.37 (bacteriostatic), 4.59 (bactericidal) and 7.99 (elimination) mg/kg. These findings indicated that the calculated recommended dose could assist in achieving more precise administration, increasing the effectiveness of DoxHcl&FF treatment for APP infections.

Tài liệu tham khảo

Aslam, B., W. Wang, M.I. Arshad, M. Khurshid, S. Muzammil, M.H. Rasool, M.A. Nisar, R.F. Alvi, M.A. Aslam, M.U. Qamar, M. Salamat, and Z. Baloch. 2018. Antibiotic resistance: A rundown of a global crisis. Infection and Drug Resistance 11: 1645–1658. https://doi.org/10.2147/IDR.S173867. Ayukekbong, J.A., M. Ntemgwa, and A.N. Atabe. 2017. The threat of antimicrobial resistance in developing countries: Causes and control strategies. Antimicrobial Resistance and Infection Control 6: 47. https://doi.org/10.1186/s13756-017-0208-x. Bao, C.T., J.M. Xiao, B.J. Liu, J.F. Liu, R.N. Zhu, P. Jiang, L. Li, P.R. Langford, and L.C. Lei. 2019. Establishment and comparison of Actinobacillus pleuropneumoniae experimental infection model in mice and piglets. Microbial Pathogenesis 128: 381–389. https://doi.org/10.1016/j.micpath.2019.01.028. Bhardwaj, P., P.K. Sidhu, S. Saini, D. MB, and S. Rampal. 2019. Pharmacokinetic-pharmacodynamic relationship of marbofloxacin for Escherichia coli and Pasturella multocida following repeated intramuscular administration in goats. Journal of Veterinary Pharmacology and Therapeutics 42 (4): 430–439. https://doi.org/10.1111/jvp.12776. Catry, B., L. Duchateau, J. Van de Ven, H. Laevens, G. Opsomer, F. Haesebrouck, and A. De Kruif. 2008. Efficacy of metaphylactic florfenicol therapy during natural outbreaks of bovine respiratory disease. Journal of Veterinary Pharmacology and Therapeutics 31 (5): 479–487. https://doi.org/10.1111/j.1365-2885.2008.00981.x. Da Silva, G.C., C.C. Rossi, M.F. Santana, P.R. Langford, J.T. Bossé, and D. Bazzolli. 2017. p518, a small floR plasmid from a south American isolate of Actinobacillus pleuropneumoniae. Veterinary Microbiology 204: 129–132. https://doi.org/10.1016/j.vetmic.2017.04.019. Fu, G., J. Peng, Y. Wang, S. Zhao, W. Fang, K. Hu, J. Shen, and J. Yao. 2016. Pharmacokinetics and pharmacodynamics of sulfamethoxazole and trimethoprim in swimming crabs (Portunus trituberculatus) and in vitro antibacterial activity against Vibrio: PK/PD of SMZ-TMP in crabs and antibacterial activity against Vibrio. Environmental Toxicology and Pharmacology 46: 45–54. https://doi.org/10.1016/j.etap.2016.06.029. Jourquin, S., J. Bokma, L. De Cremer, K. van Leenen, N. Vereecke, and B. Pardon. 2022. Randomized field trial comparing the efficacy of florfenicol and oxytetracycline in a natural outbreak of calf pneumonia using lung reaeration as a cure criterion. Journal of Veterinary Internal Medicine 36 (2): 820–828. https://doi.org/10.1111/jvim.16348. Kim, M.H., E. Gebru, Z.Q. Chang, J.Y. Choi, M.H. Hwang, E.H. Kang, J.H. Lim, H.I. Yun, and S.C. Park. 2008. Comparative pharmacokinetics of tylosin or florfenicol after a single intramuscular administration at two different doses of tylosin-florfenicol combination in pigs. The Journal of Veterinary Medical Science 70 (1): 99–102. https://doi.org/10.1292/jvms.70.99. Lei, Z., Q. Liu, J. Xiong, B. Yang, S. Yang, Q. Zhu, K. Li, S. Zhang, J. Cao, and Q. He. 2017. Pharmacokinetic and Pharmacodynamic evaluation of Marbofloxacin and PK/PD modeling against Escherichia coli in pigs. Frontiers in Pharmacology 8: 542. https://doi.org/10.3389/fphar.2017.00542. Li, X., S. Xie, Y. Pan, W. Qu, Y. Tao, D. Chen, L. Huang, Z. Liu, Y. Wang, and Z. Yuan. 2016. Preparation, characterization and pharmacokinetics of doxycycline hydrochloride and florfenicol polyvinylpyrroliddone microparticle entrapped with hydroxypropyl-β-cyclodextrin inclusion complexes suspension. Colloids and Surfaces B: Biointerfaces 141: 634–642. https://doi.org/10.1016/j.colsurfb.2016.02.027. Lima, T.B., O.N. Silva, K.C. de Almeida, S.M. Ribeiro, D.O. Motta, S. Maria-Neto, M.B. Lara, C.R. Filho, A.S. Ombredane, C. de Faria Junior, N.S. Parachin, B.S. Magalhães, and O.L. Franco. 2017. Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae. The Journal of Antibiotics 70 (2): 122–129. https://doi.org/10.1038/ja.2016.77. Liu, J., K.F. Fung, Z. Chen, Z. Zeng, and J. Zhang. 2003. Pharmacokinetics of florfenicol in healthy pigs and in pigs experimentally infected with Actinobacillus pleuropneumoniae. Antimicrobial Agents and Chemotherapy 47 (2): 820–823. https://doi.org/10.1128/AAC.47.2.820-823.2003. Louie, A., W. Liu, S. Fikes, D. Brown, and G.L. Drusano. 2013. Impact of meropenem in combination with tobramycin in a murine model of Pseudomonas aeruginosa pneumonia. Antimicrobial Agents and Chemotherapy 57 (6): 2788–2792. https://doi.org/10.1128/AAC.02624-12. Luo, W., D. Chen, M. Wu, Z. Li, Y. Tao, Q. Liu, Y. Pan, W. Qu, Z. Yuan, and S. Xie. 2019. Pharmacokinetics/pharmacodynamics models of veterinary antimicrobial agents. Journal of Veterinary Science 20 (5): e40. https://doi.org/10.4142/jvs.2019.20.e40. Maaland, M.G., M.G. Papich, J. Turnidge, and L. Guardabassi. 2013. Pharmacodynamics of doxycycline and tetracycline against staphylococcus pseudintermedius: Proposal of canine-specific breakpoints for doxycycline. Journal of Clinical Microbiology 51 (11): 3547–3554. https://doi.org/10.1128/JCM.01498-13. Mouton, J.W., U. Theuretzbacher, W.A. Craig, P.M. Tulkens, H. Derendorf, and O. Cars. 2008. Tissue concentrations: Do we ever learn? The Journal of Antimicrobial Chemotherapy 61 (2): 235–237. https://doi.org/10.1093/jac/dkm476. Mzyk, D.A., R.E. Baynes, K.M. Messenger, M. Martinez, and G.W. Smith. 2017. Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves. Journal of Veterinary Pharmacology and Therapeutics 40 (2): 179–191. https://doi.org/10.1111/jvp.12346. Nielsen, E.I., and L.E. Friberg. 2013. Pharmacokinetic-pharmacodynamic modeling of antibacterial drugs. Pharmacological Reviews 65 (3): 1053–1090. https://doi.org/10.1124/pr.111.005769. Pérez-Fernández, R., V. Cazanga, J.A. Jeldres, P.P. Silva, J. Riquelme, F. Quiroz, C. Palma, M.D. Carretta, and R.A. Burgos. 2017. Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 47 (5): 408–415. https://doi.org/10.1080/00498254.2016.1195522. Podolska, A., C. Anthon, M. Bak, N. Tommerup, K. Skovgaard, P.M. Heegaard, J. Gorodkin, S. Cirera, and M. Fredholm. 2012. Profiling microRNAs in lung tissue from pigs infected with Actinobacillus pleuropneumoniae. BMC Genomics 13: 459. https://doi.org/10.1186/1471-2164-13-459. Rivero-Juarez, A., N. Vallejo, P. Lopez-Lopez, A.I. Díaz-Mareque, M. Frias, A. Vallejo, J. Caballero-Gómez, M. Rodríguez-Velasco, E. Molina, and A. Aguilera. 2019. Ribavirin as a first treatment approach for hepatitis E virus infection in transplant recipient patients. Microorganisms 8 (1): 51. https://doi.org/10.3390/microorganisms8010051. Sassu, E.L., J.T. Bossé, T.J. Tobias, M. Gottschalk, P.R. Langford, and I. Hennig-Pauka. 2018. Update on Actinobacillus pleuropneumoniae-knowledge, gaps and challenges. Transboundary and Emerging Diseases 65 (Suppl 1): 72–90. https://doi.org/10.1111/tbed.12739. Shin, S.J., S.G. Kang, R. Nabin, M.L. Kang, and H.S. Yoo. 2005. Evaluation of the antimicrobial activity of florfenicol against bacteria isolated from bovine and porcine respiratory disease. Veterinary Microbiology 106 (1–2): 73–77. https://doi.org/10.1016/j.vetmic.2004.11.015. Toutain, P.L., J.R. del Castillo, and A. Bousquet-Mélou. 2002. The pharmacokinetic-pharmacodynamic approach to a rational dosage regimen for antibiotics. Research in Veterinary Science 73 (2): 105–114. https://doi.org/10.1016/s0034-5288(02)00039-5. Toutain, P.L., and P. Lees. 2004. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. Journal of Veterinary Pharmacology and Therapeutics 27 (6): 467–477. https://doi.org/10.1111/j.1365-2885.2004.00613.x. Yan, R., Y. Yang, and Y. Chen. 2018. Pharmacokinetics of Chinese medicines: Strategies and perspectives. Chinese Medicine 13: 24. https://doi.org/10.1186/s13020-018-0183-z. Yu, X.H., X.J. Song, Y. Cai, B.B. Liang, D.F. Lin, and R. Wang. 2010. In vitro activity of two old antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. The Journal of Antibiotics 63 (11): 657–659. https://doi.org/10.1038/ja.2010.105.
Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Tập 3

1-13

Thông tin tác giả