RESUMO
Estimation of plasma protein binding (PPB) is of paramount importance in the pharmacokinetics characterization of drugs, as it can cause significant change in volume of distribution, clearance and half-life of the drug. Ampicillin (α-amino benzyl penicillin) is most commonly used drug in equine practice. This study was conducted to determine the extent of PPB of ampicillin in apparently healthy horses (n=6). A simple spectrophotometric method was applied for the determination of ampicillin at 320 nm wavelength, based on acid degradation product of penicillin at 75°C in presence of citrate buffer (pH 5.2) and traces of copper salt. In the study, it was observed that this method permits the detection of ampicillin to a level not beyond 1.0 μg/ml. Various concentrations of ampicillin (3.125, 6.25, 12.5, 25, 50, 100 μg/ml) were prepared in triplicate in pooled plasma collected from healthy animals. In vitro binding of ampicillin to plasma proteins was determined by employing the equilibrium dialysis technique. The study revealed that the plasma protein binding of ampicillin was to the extent of 12.8 ± 0.07 %. Binding capacity of ampicillin to plasma protein (βi) and dissociation rate constant of protein-drug complex (Kβ) in the present study were 0.34 × 10-6 ± 0.02 × 10-6 mol.gm-1 and 0.003 × 10-9 ± 0.0003 × 10-9 mol, respectively in horses. Hence, the study concluded that usage of spectrophotometric method helps in quick, cost effective and efficient results in estimation of PPB for ampicillin
RESUMO
Marbofloxacin is a broad-spectrum fluoroquinolone antibiotic developed for use in veterinary medicine for the treatment of skin and soft tissue infections in dogs and cats. Plasma protein binding plays a vital role in distribution, elimination and therapeutic effectiveness of drugs. In the present study we evaluated the plasma protein binding of marbofloxacin in healthy and liver dysfunctioned buffalo calves. In vitro binding of marbofloxacin to plasma proteins was determined by employing the equilibrium dialysis technique and further analyzed by High Performance Liquid Chromatography assay. The plasma protein binding for healthy calves ranges between 25.3±0.34% to 30.4±0.40% with an overall binding of 28.66 ± 0.421%. Kinetic constants (βi) and (Kβ) was 2.6±0.12×10-8 mole/g and 1.9±0.08×10-7 mole, respectively. The percentage of plasma protein binding for liver dysfunctioned buffalo calves extended from 24.5 - 30.3% with an overall mean of 28.59 ± 0.693%. The binding capacity of the drug to plasma proteins (βi) and dissociation rate constant of protein drug complex (Kβ) were 2.53±0.13 10-5 mole/g and 1.94±0.09×10-6 mole respectively. There was no significant change observed in plasma protein binding and the kinetic constant of liver dysfunctioned buffalo calves when compared to the healthy group
RESUMO
The pharmacokinetics of intravenously administered gatifloxacin, upon concomitant administration with meloxicam was investigated in buffalo calves. Meloxicam was administered subcutaneously (0.5 mg.kg-1) immediately followed by intravenous administration of Gatifloxacin (4 mg.kg-1). The concentration of gatifloxacin was estimated in plasma by microbiological assay. Pharmacokinetic parameters were calculated and appropriate dosage schedule was computed. The therapeutic plasma drug concentration was maintained up to 12 h. Gatifloxacin was rapidly distributed from blood to tissue compartment, which was evident from the high values of distribution rate constant, α1 (11.9 ± 0.52 h-1) and the ratio of rate constant of transfer of drug from central to peripheral compartments and vice versa, K12/K21 (3.05 ± 0.36) and K13/K31 (2.04 ± 0.12). The area under the plasma drug concentration-time curve and apparent volume of distribution were 12.0 ± 0.68 µg.ml-1.h and 2.69 ± 0.14 L.kg-1, respectively. The elimination half-life (t1/2β), total body clearance (ClB) and the ratio of drug present in peripheral to central compartment (P/C) were 5.59 ± 0.40 h, 337.6 ± 19.9 ml.kg-1.h-1 and 8.04 ± 0.50, respectively. The present study revealed that the most suitable dosage regimen of gatifloxacin when concomitantly administered with meloxicam in buffalo calves would be 2.5 mg.kg-1 followed by 2.0 mg.kg-1 at 12 h intervals.
Investigou-se a farmacocinética da gatifloxacina, administrada por via intravenosa, concomitante à aplicação de meloxicam em bezerros búfalos. O meloxicam foi administrado por via subcutânea (0,5 mg.kg-1), imediatamente seguido pela administração intravenosa de gatifloxacina (4 mg.kg-1). A concentração plasmática de gatifloxacina foi estimada por ensaio microbiológico. Os parâmetros farmacocinéticos foram calculados e a posologia adequada foi computada. A concentração plasmática do fármaco-terapêutico foi mantida por 12 h. A gatifloxacina foi rapidamente distribuída a partir de sangue para o compartimento de tecido, o que ficou evidente a partir dos valores elevados da taxa constante de distribuição, α1 (11.9 ± 0.52 h-1) e a proporção de velocidade constante de transferência de droga a partir de centrais para os compartimentos periféricos e vice-versa, K12/K21 (3.05 ± 0.36) e K13/K31 (2.04 ± 0.12). A área sob a curva plasmática de concentração-tempo da droga e o volume aparente de distribuição foi de 12.0 ± 0.68 µg.ml-1.h e 2.69 ± 0.14 L.kg-1, respectivamente. A meia-vida (t1/2β), a depuração corporal total (ClB) e relação da droga presente no sangue periférico para o compartimento central (P/C) foram 5.59 ± 0.40 h, 337.6 ± 19.9 ml.kg-1.h-1 e 8.04 ± 0.50, respectivamente. O presente estudo revelou que o regime de dosagem mais adequado de gatifloxacina quando administrada concomitantemente com meloxicam em bezerros búfalos seria 2,5 mg.kg-1 seguida de 2,0 mg.kg-1 em intervalos de 12 h.