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GOUDAH, A.,ABO EL-SOOUD, K.,SHIM, J.-H.,SHIN, H.-C.,ABD EL-ATY, A. M. Blackwell Publishing Ltd 2008 JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTIC Vol.31 No.5
<P>The target of the present study was to investigate the plasma disposition kinetics of levofloxacin in stallions (<I>n</I> = 6) following a single intravenous (i.v.) bolus or intramuscular (i.m.) injection at a dose rate of 4 mg/kg bwt, using a two-phase crossover design with 15 days as an interval period. Plasma samples were collected at appropriate times during a 48-h administration interval, and were analyzed using a microbiological assay method. The plasma levofloxacin disposition was best fitted to a two-compartment open model after i.v. dosing. The half-lives of distribution and elimination were 0.21 ± 0.13 and 2.58 ± 0.51 h, respectively. The volume of distribution at steady-state was 0.81 ± 0.26 L/kg, the total body clearance (<I>Cl</I><SUB>tot</SUB>) was 0.21 ± 0.18 L/h/kg, and the areas under the concentration–time curves (<I>AUC</I>s) were 18.79 ± 4.57 &mgr;g.h/mL. Following i.m. administration, the mean <I>t</I><SUB>1/2el</SUB> and <I>AUC</I> values were 2.94 ± 0.78 h and 17.21 ± 4.36 &mgr;g.h/mL. The bioavailability was high (91.76% ± 12.68%), with a peak plasma mean concentration (<I>C</I><SUB>max</SUB>) of 2.85 ± 0.89 &mgr;g/mL attained at 1.56 ± 0.71 h (<I>T</I><SUB>max</SUB>). The <I>in vitro</I> protein binding percentage was 27.84%. Calculation of efficacy predictors showed that levofloxacin might have a good therapeutic profile against Gram-negative and Gram-positive bacteria, with an <I>MIC</I> ≤ 0.1 &mgr;g/mL.</P>
GOUDAH, A.,CHO, H.-J.,SHIN, H.-C.,SHIM, J.-H.,REGMI, N. L.,SHIMODA, M.,ABD EL-ATY, A. M. Blackwell Publishing Ltd 2009 JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTIC Vol.32 No.4
<P>The purpose of the current investigation is to elucidate the pharmacokinetic profiles of orbifloxacin (OBFX) in lactating ewes (<I>n </I>= 6) following intravenous (i.v.) and intramuscular (i.m.) administrations of 2.5 mg/kg W. In a crossover study, frequent blood, milk, and urine samples were drawn for up to 48 h after the end of administration, and were then assayed to determine their respective drug concentrations through microbiological assay using <I>Klebsiella pneumoniae</I> as the test micro-organism. Plasma pharmacokinetic parameters were derived from plasma concentration–time data using a compartmental and noncompartmental analysis, and validated a relatively rapid elimination from the blood compartment, with a slope of the terminal phase of 0.21 ± 0.02 and 0.19 ± 0.06 per hour and a half-life of 3.16 ± 0.43 and 3.84 ± 0.59 h, for i.v. and i.m. dosing, respectively. OBFX was widely distributed with a volume of distribution <I>V</I>(<SUB>d(ss)</SUB>) of 1.31 ± 0.12 L/kg, as suggested by the low percentage of protein binding (22.5%). The systemic body clearance (<I>Cl</I><SUB>B</SUB>) was 0.32 ± 0.12 L/h·kg. Following i.m. administration, the maximum plasma concentration (<I>C</I><SUB>max</SUB>) of 1.53 ± 0.34 &mgr;g/mL was reached at <I>t</I><SUB>max</SUB> 1.25 ± 0.21 h. The drug was completely absorbed after i.m. administration, with a bioavailability of 114.63 ± 11.39%. The kinetic milk <I>AUC</I><SUB>milk</SUB>/<I>AUC</I><SUB>plasma</SUB> ratio indicated a wide penetration of orbifloxacin from the bloodstream to the mammary gland. OBFX urine concentrations were higher than the concurrent plasma concentrations, and were detected up to 30 h postinjection by both routes. Taken together, these findings indicate that systemic administration of orbifloxacin could be efficacious against susceptible mammary and urinary pathogens in lactating ewes.</P>
Pharmacokinetics and Mammary Residual Depletion of Erythromycin in Healthy Lactating Ewes
Goudah, A.,Sher Shah, S.,Shin, H.C.,Shim, J.H.,Abd El-Aty, A. M. Blackwell Publishing Ltd 2007 Journal of veterinary medicine. A, Physiology, pat Vol.54 No.10
<P>Summary</P><P>The aim of this investigation was to examine the pharmacokinetics and mammary excretion of erythromycin administered to lactating ewes (<I>n</I> = 6) by the intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes at a dosage of 10 mg/kg. Blood and milk samples were collected at pre-determined times, and a microbiological assay method was used to measure erythromycin concentrations in serum and milk. The concentration–time data were analysed by compartmental and non-compartmental kinetic methods. The serum concentration–time data of erythromycin were fit to a two-compartment model after i.v. administration and a one-compartment model with first-order absorption after i.m. and s.c. administration. The elimination half-life (<I>t</I><SUB>1/2&bgr;</SUB>) was 4.502 ± 1.487 h after i.v. administration, 4.874 ± 0.296 h after i.m. administration and 6.536 ± 0.151 h after s.c. administration. The clearance value (Cl<SUB>tot</SUB>) after i.v. dosing was 1.292 ± 0.121 l/h/kg. After i.m. and s.c. administration, observed peak erthyromycin concentrations (<I>C</I><SUB>max</SUB>) of 0.918 ± 0.092 <I>&mgr;</I>g/ml and 0.787 ± 0.010 <I>&mgr;</I>g/ml were achieved at 0.75 and 1.0 h (<I>T</I><SUB>max</SUB>) respectively. The bioavailability obtained after i.m. and s.c. administration was 91.178 ± 10.232% and 104.573 ± 9.028% respectively. Erythromycin penetration from blood to milk was quick for all the routes of administration, and the high AUC<SUB>milk</SUB>/AUC<SUB>serum</SUB> (1.186, 1.057 and 1.108) and C<SUB>max‐milk</SUB>/C<SUB>max‐serum</SUB> ratios reached following i.v., i.m. and s.c. administration, respectively, indicated an extensive penetration of erythromycin into the milk.</P>