12 research outputs found
Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats
An in vivo pharmacokinetic study of metformin microparticles as an oral sustained release formulation in rabbits
This research was funded by the Government of the Region de Murcia (Spain) by the Fundacion Seneca (project 20950/PI/18). The Fundacion Seneca had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Background: Metformin hydrochloride is a biguanide derivative that has been widely used to treat type 2 diabetes
in humans. In veterinary medicine, metformin has shown increasing potential for diabetes treatment in different
species, such as equids, dogs, cats and rabbits. It is highly hydrophilic, with incomplete gastrointestinal absorption
and very large variability in absolute bioavailability between species, ranging from 4% in equids to 60% in humans.
Metformin also shows a short half-life of approximately 2 h in dogs, cats, horses and humans. The objectives of this
study were to evaluate a poly (lactic acid) (PLA) metformin microparticle formulation to test in rabbits and conduct a
pharmacokinetics study of intravenous (
SIV) and oral solution (
SPO) metformin administration and oral PLA microparticle
(
SPLA) administration to rabbits to evaluate the improvement in the metformin pharmacokinetics profile.
Results: Metformin-loaded PLA microparticles were characterized by a spherical shape and high encapsulation
efficiency. The results from Fourier transform infrared (FTIR) spectroscopy suggested the presence of interactions
between metformin and PLA. X-Ray diffraction (XRD) analysis corroborated the results from the differential scanning
calorimetry (DSC) studies, showing that metformin is present in an amorphous state within the microparticles. Physicochemical
characterization suggested that PLA and metformin hydrochloride interacted within the microparticles via
hydrogen bonding interactions. The pharmacokinetic study in rabbits showed sustained-release characteristics from
the prepared microparticles with a delay in the time needed to reach the maximum concentration (
Tmax), decreased
Cmax
and bioavailability, and increased mean residence time (MRT) and half-life compared to the pure drug solution.
Conclusions: Metformin-loaded PLA microparticles showed optimal and beneficial properties in terms of their physicochemical
characteristics, making them suitable for use in an in vivo pharmacokinetic study. The pharmacokinetic
parameters of the metformin microparticles from the in vivo study showed a shorter Tmax,
longer MRT and half-life,
decreased Cmax
and the prolonged/sustained release expected for metformin. However, the unexpected decrease in
bioavailability of metformin from the microparticles with respect to the oral solution should be evaluated for microparticle
and dose design in future works, especially before being tested in other animal species in veterinary medicine.Government of the Region de Murcia (Spain) by the Fundacion Seneca 20950/PI/1
Farmacocinética de la silimarina intravenosa en conejos, a dosis única
A kinetic survey of silymarin has been carried out after intravenous administration in rabbits. Results show that silymarin is spread in rabbits according to an open pattern with two compartiments whose expression is
Ct=25,28-e-0,1235-t+22,38-e-0,0139-tmg/l.
From this ecuation we have found out the different pharmacokinetics parameters.Se ha estudiado la cinética de la silimarina, tras su administración intravenosa a dosis única, en el conejo. Los resultados indican que la silimarina se distribuye en el conejo siguiendo un modelo bicompartimental abierto cuya expresión es
Ct=25,28-e-0,1235-t+22,38-e-0,0139-tmg/l.
A partir de dicha ecuación se han deducido los diversos parámetros farmacocinéticos
Intravenous Pharmacokinetics and binding to plasmatic proteins of Amoxycillin and Clavulanic acid in sheeps
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
Contagious agalactia is a mycoplasmosis affecting small ruminants that have become an important issue in many countries. However, PK/PD studies of antibiotics to treat this problem in lactating goats affected by Mycoplasma (M.) agalactiae, the main CA-causing mycoplasma are almost non-existent. The aims of this study were to evaluate the plasma and milk disposition of marbofloxacin in lactating goats after intravenous (IV), subcutaneous (SC) and subcutaneous poloxamer P407 formulations with and without carboxy-methylcellulose (SC-P407-CMC and SC-P407) administration. Marbofloxacin concentrations were analysed by the High Performance Liquid Chromatography (HPLC) method. Minimum inhibitory concentrations (MIC) of M. agalactiae field isolates from mastitic goat’s milk were used to calculate surrogate markers of efficacy. Terminal half-lives of marbofloxacin after IV, SC, SC-P407 and SC-P407-CMC administration were 7.12, 6.57, 13.92 and 12.19 h in plasma, and the half-lives of elimination of marbofloxacin in milk were 7.22, 7.16, 9.30 and 7.74 h after IV, SC, SC-P407 and SC-P407-CMC administration, respectively. Marbofloxacin penetration from the blood into the milk was extensive, with Area Under the Curve (AUCmilk/AUCplasma) ratios ranged 1.04–1.23, and maximum concentrations (Cmax-milk/Cmax-plasma) ratios ranged 0.72–1.20. The PK/PD surrogate markers of efficacy fAUC24/MIC and the Monte Carlo simulation show that marbofloxacin ratio (fAUC24/MIC > 125) using a 90% of target attainment rate (TAR) need a dose regimen between 8.4 mg/kg (SC) and 11.57 mg/kg (P407CMC) and should be adequate to treat contagious agalactia in lactating goats
Protein binding of Amoxycillin and Clavulanic acid in pigeons (Columba livia) and chickens (Gallus gallus)
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.
Contagious agalactia is a mycoplasmosis affecting small ruminants that have become an important issue in many countries. However, PK/PD studies of antibiotics to treat this problem in lactating goats affected by Mycoplasma (M.) agalactiae, the main CA-causing mycoplasma are almost non-existent. The aims of this study were to evaluate the plasma and milk disposition of marbofloxacin in lactating goats after intravenous (IV), subcutaneous (SC) and subcutaneous poloxamer P407 formulations with and without carboxy-methylcellulose (SC-P407-CMC and SC-P407) administration. Marbofloxacin concentrations were analysed by the High Performance Liquid Chromatography (HPLC) method. Minimum inhibitory concentrations (MIC) of M. agalactiae field isolates from mastitic goat's milk were used to calculate surrogate markers of efficacy. Terminal half-lives of marbofloxacin after IV, SC, SC-P407 and SC-P407-CMC administration were 7.12, 6.57, 13.92 and 12.19 h in plasma, and the half-lives of elimination of marbofloxacin in milk were 7.22, 7.16, 9.30 and 7.74 h after IV, SC, SC-P407 and SC-P407-CMC administration, respectively. Marbofloxacin penetration from the blood into the milk was extensive, with Area Under the Curve (AUCmilk/AUCplasma) ratios ranged 1.04-1.23, and maximum concentrations (Cmax-milk/Cmax-plasma) ratios ranged 0.72-1.20. The PK/PD surrogate markers of efficacy fAUC24/MIC and the Monte Carlo simulation show that marbofloxacin ratio (fAUC24/MIC > 125) using a 90% of target attainment rate (TAR) need a dose regimen between 8.4 mg/kg (SC) and 11.57 mg/kg (P407CMC) and should be adequate to treat contagious agalactia in lactating goats