1. PK/PD integration for intramuscular dose determination of intramuscular sodium cloxacillin for infections caused by Staphylococcus spp in goat
- Author
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L.A. Felix, L.W.F. Gonzaga, B.C.F. Soares, G. Suárez, H.M. Brandão, P.Y. Faccioli-Martins, and M. Ferrante
- Subjects
antibiotic therapy ,Monte Carlo simulation ,pharmacometrics ,sepsis ,translational model ,Animal culture ,SF1-1100 - Abstract
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.
- Published
- 2023
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