Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels
Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the tempera...
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| Published in | Journal of fish diseases Vol. 42; no. 8; pp. 1181 - 1190 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Blackwell Publishing Ltd
01.08.2019
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg−1 day−1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study. |
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| AbstractList | Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg−1 day−1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study. Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg −1 day −1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed C min(ss) while at 28 and 32°C underestimation of the C min(ss) in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study. Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg−1 day−1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study. Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug-related side effects. The current study established a pharmacokinetic-pharmacodynamic (PK-PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature-dependent PK and the pathogen-dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg-1 day-1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose-dependent manner was observed and likely due to the occurrence of non-linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK-PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non-linearity of FF in tilapia warrant further study.Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug-related side effects. The current study established a pharmacokinetic-pharmacodynamic (PK-PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature-dependent PK and the pathogen-dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg-1 day-1 (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cmin(ss) while at 28 and 32°C underestimation of the Cmin(ss) in a dose-dependent manner was observed and likely due to the occurrence of non-linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK-PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non-linearity of FF in tilapia warrant further study. Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug-related side effects. The current study established a pharmacokinetic-pharmacodynamic (PK-PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature-dependent PK and the pathogen-dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg day (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed C while at 28 and 32°C underestimation of the C in a dose-dependent manner was observed and likely due to the occurrence of non-linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK-PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non-linearity of FF in tilapia warrant further study. Optimized dosing regimen is key to the effective use of antibacterials and to minimizing drug‐related side effects. The current study established a pharmacokinetic–pharmacodynamic (PK‐PD) model for the determination of optimal antibacterial dosing regimen in fish taken into consideration the temperature‐dependent PK and the pathogen‐dependent antimicrobial susceptibility, using florfenicol (FF) in Nile tilapia as an example. The calculated optimal dosages significantly varied by temperature and target MIC levels, ranging from 2.23 (MIC 1 µg/ml at 24°C) to 34.88 mg kg⁻¹ day⁻¹ (MIC 4 µg/ml at 32°C). The appropriateness of the calculated dosages was successfully verified by the in vivo studies. After 5 days of oral administration of the calculated optimal dosage at 24°C, the predicted plasma drug values were in line with the mean observed Cₘᵢₙ₍ₛₛ₎ while at 28 and 32°C underestimation of the Cₘᵢₙ₍ₛₛ₎ in a dose‐dependent manner was observed and likely due to the occurrence of non‐linear PK at high dosages. The averaged serum protein binding of FF was 19.1%. Our results demonstrated the appropriateness and clinical applicability of the developed PK‐PD approach for the determination of optimal dosing regimens at given temperatures and MICs. Saturation metabolism and PK non‐linearity of FF in tilapia warrant further study. |
| Author | Rairat, Tirawat Hsieh, Chia‐Yu Thongpiam, Wipavee Chou, Chi‐Chung |
| Author_xml | – sequence: 1 givenname: Tirawat surname: Rairat fullname: Rairat, Tirawat organization: National Chung Hsing University – sequence: 2 givenname: Chia‐Yu surname: Hsieh fullname: Hsieh, Chia‐Yu organization: National Chung Hsing University – sequence: 3 givenname: Wipavee surname: Thongpiam fullname: Thongpiam, Wipavee organization: National Chung Hsing University – sequence: 4 givenname: Chi‐Chung orcidid: 0000-0002-4622-2552 surname: Chou fullname: Chou, Chi‐Chung email: ccchou@nchu.edu.tw organization: National Chung Hsing University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31157416$$D View this record in MEDLINE/PubMed |
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| Keywords | pharmacokinetic-pharmacodynamic Nile tilapia florfenicol optimal dosing regimen |
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| SubjectTerms | adverse effects antibiotic resistance Antibiotics Antiinfectives and antibacterials blood proteins Dosage dose response Drug dosages Drugs Fish Florfenicol Freshwater fishes In vivo methods and tests in vivo studies Linearity Marine fishes Metabolism Minimum inhibitory concentration Nile tilapia optimal dosing regimen Oral administration Oreochromis niloticus Pathogens Pharmacodynamics Pharmacokinetics pharmacokinetic–pharmacodynamic Pharmacology Ponds protein binding Saturation Serum Side effects Temperature Temperature dependence Tilapia Water temperature |
| Title | Pharmacokinetic–pharmacodynamic modelling for the determination of optimal dosing regimen of florfenicol in Nile tilapia (Oreochromis niloticus) at different water temperatures and antimicrobial susceptibility levels |
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