This study describes disposition of long-acting moxifloxacin and conventional formulations of moxifloxacin in sheep after intravenous administration in five male sheep. Long acting moxifloxacin solution (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin (10%) were injected in jugular vein. Blood samples were collected from contralateral jugular vein in test tubes containing 30–50 IU heparin (anticoagulant) periodically from 0.083 to 72 h of drug administration. Drug concentrations in plasma were determined using High-Performance Liquid Chromatography (HPLC) with fluorescence detector. The mobile phase consisted of a mixture of buffer (10 gm of tetrabutyl ammonium hydrogen sulphate per liter-deionised water) and acetonitrile (80 : 20). The buffer was 0.067M of disodium hydrogen phosphate with pH of 7.5. The flow rate was 1 mL·min−1 at ambient temperature. The effluent was monitored at 296 nm excitation and 504 nm emissions wavelength. HPLC with fluorescence detector method for plasma moxifloxacin assay was standardized with specific modification for plasma of sheep in the present study. After single-dose intravenous administration of long acting moxifloxacin the plasma concentration of 0.016 ± 0.001
Moxifloxacin is a new 8-methoxy-quinolone with a broad spectrum of antibacterial activity against organisms Gram-positive and Gram-negative bacteria, anaerobes, and atypical organism such as
Five healthy adult male sheep weighing 38–45 kg were used in the present study. Sheep were housed at Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar. The sheep were housed in well-ventilated appropriately spaced animal shed and fed with good quality fodder and concentration. Animals had free access to clean and potable water during course of experiment. All animals were acclimatized for the period of 15 days and observed clinically daily to confirm any illness or disease. Animals were not treated earlier by any drugs. The experimental protocol was approved by IAEC and all the measures for the well being of experiment animal were taken as per CPCSEA guideline.
Long acting moxifloxacin (10% moxifloxacin in solution with L-arginine, N-butyl alcohol, and benzyl alcohol) and conventional moxifloxacin injectable solution, moxifloxacin-base powder for standardization, were obtained from INTAS Animal Health, Gujarat, India. Water, acetonitrile, and tetrabutyl ammonium hydrogen sulfate of HPLC grade were purchased from S. D. Fine Chem. Ltd, Mumbai. 0.067 M disodium hydrogen phosphate and hydrochloric acid of analytical grade were purchased from S. D. Fine Chem. Ltd, Mumbai.
Five sheep were administered conventional and long acting moxifloxacin formulation at the dose rate of 5.5 and 7.5 mg
Plasma concentrations of moxifloxacin were measured using a modified HPLC method previously reported by Siefert et al. (1999) [
The HPLC separation was performed with an injection a reserve phase C18 (Supelco, 5
The mean recovery of long acting moxifloxacin from plasma was 85.14% at 25 ng/mL. The sensitivity of long acting moxifloxacin assay was 25 ng
The mean (±SE) plasma concentrations of conventional and long acting moxifloxacin following single-dose intravenous administration are tabulated in Table
Plasma concentrations of conventional long acting moxifloxacin after single-dose intravenous administration in male sheep.
Time after drug administration (h) | Long acting moxifloxacin concentration ( |
Conventional moxifloxacin concentration ( |
---|---|---|
0.083 | 7.227 ± 0.130 | 9.917 ± 0.902 |
0.166 | 5.646 ± 0.044 | 5.596 ± 0.092 |
0.5 | 4.283 ± 0.220 | 3.887 ± 0.278 |
1 | 2.853 ± 0.136 | 2.496 ± 0.007 |
2 | 2.230 ± 0.055 | 1.529 ± 0.111 |
4 | 1.711 ± 0.077 | 0.544 ± 0.012 |
8 | 0.772 ± 0.022 | 0.224 ± 0.019 |
12 | 0.368 ± 0.019 | 0.067 ± 0.008 |
24 | 0.150 ± 0.002 | 0.015 ± 0.005 |
36 | 0.076 ± 0.002 | |
48 | 0.043 ± 0.001 | |
60 | 0.026 ± 0.001 | |
72 | 0.016 ± 0.002 | |
96 | ND |
ND: not detectable; figures of moxifloxacin concentrations are in mean ± S.E.
Plasma concentrations of conventional and long-acting moxifloxacin after single-doseintravenous administration in male sheep.
Initially, the conventional moxifloxacin plasma level was
The initial plasma drug concentration of long acting moxifloxacin was
While conventional moxifloxacin administration resulted in rapid decline in plasma concentration and the drug was not detectable after 24 hours of administration. This requires frequent administration of drug on daily basis. This would be costly and time consuming. The long acting moxifloxacin administration provided effective therapeutic concentration for up to 72 hours after single-dose administration. This dose is advantageous with respect to cost of treatment and compliance to animal owner. Conversely, while applying long acting moxifloxacin in sheep, initially the levels of drug remained low (7.227