PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Experimental Design
2.3. Long-Acting Formulation Preparation
2.4. Analytical Method
2.5. MICs Determination
2.6. Pharmacokinetic Analysis
2.7. PK/PD Analysis
2.8. Statistical Analysis
3. Results
3.1. Pharmacokinetic Analysis
3.2. M. agalactiae MICs Determination
3.3. PK/PD Analysis and Monte Carlo Simulation
4. Discussion
4.1. Pharmacokinetic Analysis
4.2. MICs Determination and PK/PD Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameters | IV | SC | SC-P407 | SC-PCMC |
---|---|---|---|---|
λz (1/h) | 0.10 (0.08–0.15) | 0.11 (0.09–0.15) | 0.05 (0.03–0.08) a,b | 0.06 (0.014–0.08) a,b |
t1/2λz (h) | 7.12 (4.72–9.13) | 6.57 (4.68–7.79) | 13.92 (8.99–24.42) a,b | 12.19 (8.86–17.14) a,b |
Cmax (mg/L) | 2.37 (1.04–2.75) | 2.62 (1.74–4.06) | 1.99 (1.54–2.95) | |
Tmax (h) | 1.00 (1.00–1.50) | 3.00 (2.00–4.00) b | 4.00 (2.00–6.00) b | |
AUC0-inf (mg·h/L) | 6.82 (5.53–8.93) | 8.86 (4.06–12.00) | 21.99 (17.73–27.78) | 17.24 (13.47–20.00) |
AUC24 (mg·h/L) | 6.82 (5.53–8.93) | 8.74 (3.92–11.71) | 20.25 (16.33–26.53) | 16.48 (12.95–19.02) |
MRT (h) | 3.05 (2.20–3.56) | 4.04 (3.35–4.87) | 9.63 (6.15–10.21) a,b | 7.69 (7.07–9. 11) a,b |
MAT (h) | 1.54 (0.19–1.80) | 6.49 (2.59–7.18) b | 5.35 (4.25–5.56) b | |
VSS (L/kg) | 0.91 (0.75–1.14) | |||
Cl (L/h/kg) | 0.29 (0.22–0.35) | |||
F% | 93.92 (64.91–113.40) | 103.27 (69.19–117.10) | 81.74 (68.31–106.47) |
Parameters | IV | SC | SC-P407 | SC-P407-CMC |
---|---|---|---|---|
λz (1/h) | 0.10 (0.06–0.18) | 0.10 (0.07–0.14) | 0.07 (0.04–0.12) a,b | 0.09 (0.06–0.12) a,b |
t1/2λz (h) | 7.22 (3.87–11.37) | 7.16 (4.83–9.68) | 9.30 (86.00–17.44) a,b | 7.74 (6.02–11.16) a,b |
Cmax (µg/mL) | 1.78 (0.71–2.67) | 1.41 (0.85–3.14) | 3.26 (1.46–4.63) | 2.38 (1.78–2.66) |
Tmax (h) | 2.00 (1.00–4.00) | 2.00 (2.00–4.00) | 4.00 (2.00–6.00) a,b | 4.00 (2.00–6.00) a,b |
AUC (µg·h/mL) | 7.98 (4.45–11.61) | 6.96 (4.15–14.08) | 23.36 (14.84–35.54) | 19.34 (16.09–28.08) |
AUC24 (µg·h/mL) | 7.83 (4.31–11.52) | 6.84 (4.05–13.87) | 22.89 (14.28–34.92) | 18.93 (15.79–26.41) |
MRT (h) | 4.79 (4.28–5.80) | 5.05 (4.62–5.62) | 7.73 (6.62–8.68) a,b | 7.85 (6.27–10.43) a,b |
Cmax-milk/Cmax-plasma | 0.72 (0.47–1.51) | 1.20 (0.47–1.89) | 1.11 (0.90–1.50) | |
AUCmilk/AUCplasma | 1.04 (0.79–1.37) | 0.93 (0.72–1.59) | 0.95 (0.76–1.68) | 1.23 (0.81–1.59) |
Recovery (%) | 0.76 (0.11–2.69) | 0.59 (0.24–1.34) | 0.60 (0.51–1.52) | 0.52 (0.40–0.76) |
Plasma | IV | SC | SC-P407 n | SC-P407-CMC n |
---|---|---|---|---|
Cmax (mg/L) | 2.37 (1.04–2.75) | 0.87 (0.58–1.35) b | 0.66 (0.51–0.98) b | |
AUC (mg·h/L) | 6.82 (5.53–8.93) | 8.86 (4.06–12.00) | 7.33 (5.91–9.26) | 5.75 (4.49–6.67) a,b,c |
AUC24 (mg·h/L) | 6.82 (5.53–8.93) | 8.74 (3.92–11.71) | 6.75 (5.44–8.84) | 5.49 (4.32–6.34) a,b,c |
Milk | IV | SC | SC-P407 n | SC-P407-CMC n |
Cmax (mg/L) | 1.78 (0.71–2.67) | 1.41 (0.85–3.14) | 1.09 (0.49–1.54) | 0.79 (0.59–0.89) b |
AUC (mg·h/L) | 7.98 (4.45–11.61) | 6.96 (4.15–14.08) | 7.79 (4.95–11.85) | 6.45 (5.36–9.36) |
AUC24 (mg·h/L) | 7.83 (4.31–11.52) | 6.84 (4.05–13.87) | 7.63 (4.76–11.64) | 6.31 (5.26–8.80) |
Parameters | IV | SC | SC-P407 | SC-P407-CMC |
---|---|---|---|---|
AUC24/MIC50 (h) plasma | 27.27 (22.13–35.70) | 34.94 (15.69–46.82) | 81.02 (65.33–106.12) a | 95.92 (51.79–76.08) a |
AUC24/MIC50 (h) milk | 31.32 (17.25–46.08) | 27.35 (16.22–55.47) | 91.55 (57.12–139.70) a | 75.70 (63.15–105.66) a |
AUC24/MIC90 (h) plasma | 6.82 (5.53–8.93) | 8.74 (3.92–11.71) | 20.25 (16.33–26.53) a | 16.48 (12.95–19.02) a |
AUC24/MIC90n (h) milk | 7.83 (4.31–11.52) | 6.84 (4.05–13.87) | 22.89 (14.28–34.92) a | 18.93 (15.79–26.41) a |
MIC50 (μg/mL) | 0.25 | Range (μg/mL) 0.0625–4.00 | ||
MIC90 (μg/mL) | 1.00 |
Dosage Calculated to Achieve a 90% PTA of Endpoint | ||||
---|---|---|---|---|
AUC/MIC Ratio | IV | SC | P407 | P407CMC |
125 | 9.65 | 8.47 | 8.83 | 11.57 |
50 | 3.85 | 3.48 | 3.45 | 4.61 |
30 | 2.81 | 2.44 | 2.35 | 3.2 |
25 | 1.96 | 2.27 | 1.73 | 2.3 |
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Fernández-Varón, E.; García-Romero, E.; Serrano-Rodríguez, J.M.; Cárceles, C.M.; García-Galán, A.; Cárceles-García, C.; Fernández, R.; Muñoz, C.; de la Fe, C. PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration. Animals 2021, 11, 1104. https://doi.org/10.3390/ani11041104
Fernández-Varón E, García-Romero E, Serrano-Rodríguez JM, Cárceles CM, García-Galán A, Cárceles-García C, Fernández R, Muñoz C, de la Fe C. PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration. Animals. 2021; 11(4):1104. https://doi.org/10.3390/ani11041104
Chicago/Turabian StyleFernández-Varón, Emilio, Edgar García-Romero, Juan M. Serrano-Rodríguez, Carlos M. Cárceles, Ana García-Galán, Carlos Cárceles-García, Rocío Fernández, Cristina Muñoz, and Christian de la Fe. 2021. "PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration" Animals 11, no. 4: 1104. https://doi.org/10.3390/ani11041104
APA StyleFernández-Varón, E., García-Romero, E., Serrano-Rodríguez, J. M., Cárceles, C. M., García-Galán, A., Cárceles-García, C., Fernández, R., Muñoz, C., & de la Fe, C. (2021). PK/PD Analysis of Marbofloxacin by Monte Carlo Simulation against Mycoplasmaagalactiae in Plasma and Milk of Lactating Goats after IV, SC and SC-Long Acting Formulations Administration. Animals, 11(4), 1104. https://doi.org/10.3390/ani11041104