Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

Luo, Wanhe; Chen, Dongmei; Wu, Miao; Li, Zhenxia; Tao, Yanfei; Liu, Qianying; Pan, Yuanhu; Qu, Wei; Zhang, Yuan; Xie, Shuyu

doi:10.4142/jvs.2019.20.e40

Cited by 18 publications

(17 citation statements)

References 60 publications

(76 reference statements)

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“…This model can be useful to assess the exposure-response relationship against the predominant bacterial population of a single antibiotic, and to evaluate PD drug interactions of antibiotic combinations [20]. The concentration range of the antibiotic, the composition of the culture medium, and the initial size of the bacterial inoculum are key factors [23]. The concentration range must include an antibacterial agent's concentration that does not kill any bacteria, as well as a concentration that completely kills the bacteria.…”

Section: Static Assaysmentioning

confidence: 99%

“…The effect of virulence, immune function, the injection of the test microorganism, and the antibiotic concentration at the infection site are the main determining factors. The most impor-tant disadvantage of the in vivo models is that the drug concentration cannot be quickly measured [23].…”

Section: In Vivo Animal Modelsmentioning

confidence: 99%

“…Antimicrobial agents are the most frequently used drugs in veterinary medicine [23], being the antimicrobial consumption by animals is twice than that used by humans [131]. There is no doubt about their usefulness to prevent disease and to promote growth in food animals, providing healthy animal-source food [132].…”

Section: Application Of Pk/pd Modeling In Veterinary Medicinementioning

confidence: 99%

“…There is no doubt about their usefulness to prevent disease and to promote growth in food animals, providing healthy animal-source food [132]. However, the abuse and the misuse of antimicrobials in veterinary medicine have led to higher rates of treatment failure and to the development and dissemination of bacterial resistance [23]. Therefore, all efforts have to be undertaken to reduce the consumption of antimicrobials in veterinary and to use them reasonably, and the same principles deserve to be applied in veterinary medicine as well as in human medicine.…”

Section: Application Of Pk/pd Modeling In Veterinary Medicinementioning

confidence: 99%

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The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

2021

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Pharmacokinetic/pharmacodynamic (PK/PD) analysis has proved to be very useful to establish rational dosage regimens of antimicrobial agents in human and veterinary medicine. Actually, PK/PD studies are included in the European Medicines Agency (EMA) guidelines for the evaluation of medicinal products. The PK/PD approach implies the use of in vitro, ex vivo, and in vivo models, as well as mathematical models to describe the relationship between the kinetics and the dynamic to determine the optimal dosing regimens of antimicrobials, but also to establish susceptibility breakpoints, and prevention of resistance. The final goal is to optimize therapy in order to maximize efficacy and minimize side effects and emergence of resistance. In this review, we revise the PK/PD principles and the models to investigate the relationship between the PK and the PD of antibiotics. Additionally, we highlight the outstanding role of the PK/PD analysis at different levels, from the development and evaluation of new antibiotics to the optimization of the dosage regimens of currently available drugs, both for human and animal use.

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Section: Static Assaysmentioning

confidence: 99%

Section: In Vivo Animal Modelsmentioning

confidence: 99%

Section: Application Of Pk/pd Modeling In Veterinary Medicinementioning

confidence: 99%

Section: Application Of Pk/pd Modeling In Veterinary Medicinementioning

confidence: 99%

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The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

2021

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“…Antimicrobials are indispensable pharmaceuticals to treat bacterial infections. However, for decades, antibiotics have been overused in clinic, agriculture and animal production setting, generating a strong selection pressure over bacterial species [ 1 , 2 ]. The ultimate consequence has been the emergence and dissemination of antimicrobial resistant strains among humans, animals and the environment, culminating in the rise of the global health problem of antibiotic resistance, one of the top major threats to global public health of the 21st century [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

et al. 2021

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Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

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Pharmacokinetic behaviour and pharmacokinetic–pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations

Altan,

Corum,

Durna Corum

et al. 2024

Veterinary Medicine & Sci

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ObjectiveDoxycycline (DO) has been used in fish for a long time, but there are some factors that have not yet been clarified regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties. Therefore, the aim of this study was to investigate the PK and PK/PD targets of DO after 20 mg/kg intravascular (IV), intramuscular (IM) and oral (OR) gavage administration in rainbow trout (Oncorhynchus mykiss).MethodsPlasma samples were collected at specific time points and subsequently analysed by HPLC‐ultraviolet. The PK/PD indices were calculated based on the MIC90 (Aeromonas hydrophila and Aeromonas sobria) values obtained for the respective bacteria and the PK parameters obtained for DO following both IM and OR administration.ResultsAfter IV administration, the elimination half‐life (t1/2ʎz), area under the concentration vs. time curve (AUC), apparent volume of distribution at steady‐state and total body clearance of DO were 34.81 h, 723.82 h µg/mL, 1.24 L/kg and 0.03 L/kg/h, respectively. The t1/2λz of the DO was found to be 37.39 and 39.78 h after IM, and OR administration, respectively. The bioavailability was calculated 57.02% and 32.29%, respectively, after IM and OR administration. The MIC90 of DO against A. hydrophila and A. sobria was 4 µg/mL. The PK/PD integration showed that DO (20 mg/kg dose) for A. hydrophila and A. sobria with MIC90 ≤4 µg/mL achieved target AUC/MIC value after IM administration.ConclusionsThese results suggest that when rainbow trout was treated with 20 mg/kg IV and IM administered DO, therapeutically effective concentrations were reached in the control of infections caused by A. hydrophila and A. sobria.

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Pharmacokinetics/Pharmacodynamics models of veterinary antimicrobial agents

Cited by 18 publications

References 60 publications

The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

The Role of PK/PD Analysis in the Development and Evaluation of Antimicrobials

Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Pharmacokinetic behaviour and pharmacokinetic–pharmacodynamic integration of doxycycline in rainbow trout (Oncorhynchus mykiss) after intravascular, intramuscular and oral administrations

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