Plasma pharmacokinetics and milk levels of ceftriaxone following single intravenous administration in healthy and endometritic cows.

Pharmacokinetics and milk levels of ceftriaxone were studied in healthy and endometritic cows following single intravenous administration. The drug was detected up to 8 h of dosing in plasma of healthy and endometritic cows and the drug disposition followed three-compartment open model. The values of Vd(area), AUC, t(1/2beta), Cl(B), MRT and P/C ratio were 0.50 +/- 0.19 L.kg(-1), 62.2 +/- 23.3 microg.ml(-1).h, 1.02 +/- 0.07 h, 0.30 +/- 0.09 L.kg(-1).h(-1), 1.55 +/- 0.25 h and 0.52 +/- 0.27, respectively, in healthy and 1.55 +/- 0.52 L.kg(-1), 37.0 +/- 17.1 microg.ml(-1).h, 1.56 +/- 0.25 h, 0.56 +/- 0.14 L.kg(-1).h(-1), 2.14 +/- 0.34 h and 1.44 +/- 0.60, respectively, in endometritic cows. The drug was detected in milk for 36 h after administration. For MIC(90) of 0.5 microg.ml(-1) the most appropriate dosage for ceftriaxone, would be 9.0 mg.kg(-1) repeated at 6 h intervals for the treatment of endometritis in cows.

C-3 alkyl/arylalkyl-2,3-dideoxy hex-2-enopyranosides as antitubercular agents: synthesis, biological evaluation, and QSAR study.

A series of C-3 alkyl and arylalkyl 2,3-dideoxy hex-2-enopyranoside derivatives were synthesized by Morita-Baylis-Hillman reaction using enulosides 4, 5, and 6 and various aliphatic and aromatic aldehydes. The compounds were evaluated in vitro for the complete inhibition of growth of Mycobacterium tuberculosis H37Rv. They exhibited moderate to good activity in the range of 25-1.56 mug/mL. Among these, 4d, 4h, 5c, and 4hr showed activity at minimum inhibitory concentrations, 3.12, 6.25, 1.56, and 1.56 mug/mL, respectively. These compounds were safe against cytotoxicity in VERO cell line and mouse macrophage cell line J 744A.1. A QSAR analysis by CP-MLR with alignment-free 3D-descriptors indicated the relevance of structure space comparable to the minimum energy conformation (from conformational analysis) of 5c to the activity. The study indicates that the compounds attaining the conformational space of 5c and reflecting some symmetry, minimum eccentricity, and closely placed geometric and electronegativity centers therein are favorable for activity.

Effect of substituents on diarylmethanes for antitubercular activity.

Aminoalkyl derivatives of diarylmethanes were prepared using Grignard, Friedel-Crafts arylation and aminohydrochloride chain formation reactions. These series of compounds were evaluated against Mycobacterium tuberculosis H(37)R(v) and showed the activity in the range of 6.25-25 microg/mL. Effect of heteroaryl, anthracenyl and phenanthrene groups on diarylmethane pharmacophores for antitubercular activity is described.

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 MIC90 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.

Synthesis and antitubercular activity of 2-hydroxy-aminoalkyl derivatives of diaryloxy methano phenanthrenes.

A series of 2-hydroxy-aminoalkyl derivatives of diaryloxy methano phenanthrenes were synthesized from nucleophilic opening of oxirane with different amines. These compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H(37)R(v) in vitro and showed MIC in the range of 3.12-25microg/ml.

Diaryloxy methano phenanthrenes: a new class of antituberculosis agents.

A new series of diaryloxy methano phenanthrenes were prepared through tertiary-aminoalkylations of [(methoxy-phenyl)-phenanthren-9-yl-methyl]-phenols obtained from Friedel-Crafts alkylations on (methoxy-phenyl)-phenanthren-9-yl-methanols. These series of compounds were evaluated against Mycobacterium tuberculosis H37Rv and showed the desired activity in the range of 6.25 microg/mL in vitro. One of the compound 12j protects the mice from the challenge of M. tuberculosis in vivo, as 30% of the mice were survived at treatment of 50 mg/kg body weight.