Disposition kinetics and dosage regimen of levofloxacin on concomitant administration with paracetamol in crossbred calves

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 +/- 0.36 microgram/ml, which rapidly declined to 6.39 +/- 0.16 microgram/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, alpha (17.3 +/- 1.65 /h) and the ratio of K12/K21 (1.83 +/- 0.12). The values of AUC and Vdarea were 12.7 +/- 0.12 microgram.h/ml and 0.63 +/- 0.01 l/kg. The high ratio of the AUC/MIC (126.9 +/- 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 +/- 0.01 h, 1.88 +/- 0.01 h and 0.32 +/- 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.

Disposition kinetics and urinary excretion of cefpirome after intravenous injection in buffalo calves

We investigated the disposition kinetics and urinary excretion of cefpirome in buffalo calves after a single intravenous administration of 10 mg/kg. Also, an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of cefpirome in the plasma was 57.4 +/- 0.72 microgram/ml, which declined to 0.22 +/- 0.01 microgram/ml at 24 h. The cefpirome was rapidly distributed from the blood to the tissue compartment as shown by the high distribution coefficient values (8.67 +/- 0.46/h), and by the drug's rate of transfer constant from the central to the peripheral compartment, K12 (4.94 +/- 0.31/h). The elimination halflife and the volume of distribution were 2.14 +/- 0.02 h and 0.42 +/- 0.005 l/kg, respectively. Once the distribution equilibrium was reached between the tissues and plasma, the total body clearance (ClB) and the ratio of the drug present in the peripheral to the central compartment (T/P ratio) were 0.14 +/- 0.002 l/kg/h and 1.73 +/- 0.06, respectively. Based on the pharmacokinetic parameters we obtained, an appropriate intravenous cefpirome dosage regimen for treating cefpiromesensitive bacteria in buffalo calves would be 8.0 mg/kg repeated at 12 h intervals for 5 days, or until persistence of the bacterial infection occurred.

Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following a single intramuscular administration in cross bred calves

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 +/- 0.06 microgram/ml) was detected at 1 min after injection and the peak plasma level of 3.07 +/- 0.08 microgram/ml was observed at 1 h. The drug level above MIC(90) in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 +/- 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 +/- 12.4%. The high value of AUC (7.66 +/- 0.72 mg.h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd(area) (1.02 +/- 0.05 l/kg). The high ratio of AUC/MIC (76.6 +/- 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 +/- 0.4 h and 5.57 +/- 0.51 h, respectively. The total body clearance (Cl(B)) was 204.9 +/- 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.