PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat
ABSTRACT This study aims to determine therapeutic protocols of intramuscular sodium cloxacillin (IM) in goats with potential antibacterial effects against Staphylococcus spp. We constructed a pharmacokinetic (PK) model of IM, followed by a pharmacokinetic/pharmacodynamic integration (PK/PD). Simulat...
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| Format: | Article |
| Language: | English |
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Universidade Federal de Minas Gerais
2023-11-01
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| Series: | Arquivo Brasileiro de Medicina Veterinária e Zootecnia |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-09352023000601087&lng=en&tlng=en |
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| author | L.A. Felix L.W.F. Gonzaga B.C.F. Soares G. Suárez H.M. Brandão P.Y. Faccioli-Martins M. Ferrante |
| author_facet | L.A. Felix L.W.F. Gonzaga B.C.F. Soares G. Suárez H.M. Brandão P.Y. Faccioli-Martins M. Ferrante |
| author_sort | L.A. Felix |
| collection | DOAJ |
| description | ABSTRACT This study aims to determine therapeutic protocols of intramuscular sodium cloxacillin (IM) in goats with potential antibacterial effects against Staphylococcus spp. We constructed a pharmacokinetic (PK) model of IM, followed by a pharmacokinetic/pharmacodynamic integration (PK/PD). Simulations of different therapeutic protocols were then performed, with the doses ranging from 30 to100 mg/kg every 8, 12, or 24 hours. We calculated the probability to target attainment (PTA) of reach protocol's therapeutic according to the minimum inhibitory concentration (MIC) range of 0.06 to 4 μg/mL. The PK/PD index (PDT) used was "time above the MIC for 40% of the time" (T>MIC ≥40%). Protocols with single administration per day were incapable of achieving PTA ≥ 90% for any of the estimated MICs. However, by decreasing the administration interval, the PTA was increased. Thus, from the dose of 50 mg/kg every 12 hours, a PTA≥ 90% for MICs ≤ 0.5 μg/mL was achieved, while the 30 mg/kg dose every 8 hours was able to achieve a PTA≥ 90% for MICs of 2 μg/mL. The results suggest using 30 mg/kg dose every 8 hours in clinical studies of agents with MICs ≤ 2μg/mL; Nevertheless, the practitioner should adjust the dose in severe patients. |
| first_indexed | 2024-03-11T10:43:56Z |
| format | Article |
| id | doaj.art-520442b48392477aa4a0b43b5d53652e |
| institution | Directory Open Access Journal |
| issn | 1678-4162 |
| language | English |
| last_indexed | 2024-03-11T10:43:56Z |
| publishDate | 2023-11-01 |
| publisher | Universidade Federal de Minas Gerais |
| record_format | Article |
| series | Arquivo Brasileiro de Medicina Veterinária e Zootecnia |
| spelling | doaj.art-520442b48392477aa4a0b43b5d53652e2023-11-14T07:49:57ZengUniversidade Federal de Minas GeraisArquivo Brasileiro de Medicina Veterinária e Zootecnia1678-41622023-11-017561087109610.1590/1678-4162-12944PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goatL.A. Felixhttps://orcid.org/0000-0002-1758-372XL.W.F. Gonzagahttps://orcid.org/0000-0002-3828-7321B.C.F. Soareshttps://orcid.org/0000-0002-7444-3600G. Suárezhttps://orcid.org/0000-0003-2452-3546H.M. Brandãohttps://orcid.org/0000-0002-7405-3928P.Y. Faccioli-Martinshttps://orcid.org/0000-0002-7111-1264M. Ferrantehttps://orcid.org/0000-0001-6979-2956ABSTRACT This study aims to determine therapeutic protocols of intramuscular sodium cloxacillin (IM) in goats with potential antibacterial effects against Staphylococcus spp. We constructed a pharmacokinetic (PK) model of IM, followed by a pharmacokinetic/pharmacodynamic integration (PK/PD). Simulations of different therapeutic protocols were then performed, with the doses ranging from 30 to100 mg/kg every 8, 12, or 24 hours. We calculated the probability to target attainment (PTA) of reach protocol's therapeutic according to the minimum inhibitory concentration (MIC) range of 0.06 to 4 μg/mL. The PK/PD index (PDT) used was "time above the MIC for 40% of the time" (T>MIC ≥40%). Protocols with single administration per day were incapable of achieving PTA ≥ 90% for any of the estimated MICs. However, by decreasing the administration interval, the PTA was increased. Thus, from the dose of 50 mg/kg every 12 hours, a PTA≥ 90% for MICs ≤ 0.5 μg/mL was achieved, while the 30 mg/kg dose every 8 hours was able to achieve a PTA≥ 90% for MICs of 2 μg/mL. The results suggest using 30 mg/kg dose every 8 hours in clinical studies of agents with MICs ≤ 2μg/mL; Nevertheless, the practitioner should adjust the dose in severe patients.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-09352023000601087&lng=en&tlng=enantibiotic therapyMonte Carlo simulationpharmacometricssepsistranslational model |
| spellingShingle | L.A. Felix L.W.F. Gonzaga B.C.F. Soares G. Suárez H.M. Brandão P.Y. Faccioli-Martins M. Ferrante PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat Arquivo Brasileiro de Medicina Veterinária e Zootecnia antibiotic therapy Monte Carlo simulation pharmacometrics sepsis translational model |
| title | PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat |
| title_full | PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat |
| title_fullStr | PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat |
| title_full_unstemmed | PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat |
| title_short | PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat |
| title_sort | pk pd integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by staphylococcus spp in goat |
| topic | antibiotic therapy Monte Carlo simulation pharmacometrics sepsis translational model |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-09352023000601087&lng=en&tlng=en |
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