الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
In the present work, the pharmacokinetic profiles of josamycin, trimethoprim and their combination was studied following orally and intramuscular administration in 71 normal fowls. Bioavailability of josamycin were calcula-ted in normal fowls after oral and intramuscular adminis-tration. The concentrations of josamycin and trimethoprim in serum and tissues were assayed microbiologically and chemically respectively. Josamycin:
Following a single oral administration of josamycin (18 mg/kg b.wt) in normal fowls, a maximum serum concentr-ation was recorded at 2 hours, with half-life of absorption [t0.5(ab)] valued with 0.77 h. The elimination half-life
[t0.5(0] was 2.85 h. Following a single intravenous injection of (18 mg/kg b.wt) in normal fowls previously given the same dose of josamycin orally,
the drug obayed a two-compartments open model with half-life of distribution [t0.5()] of 0.27 h., [V1 ]’ [V2 ] and [Vdss] were equal to 163.17, 166.50 and 329.67 ml/kg, respectively. The mean systemic bioavailability following oral dose was 33.88%. During repeated oral administrations of 18 mg/kg b.wt once daily for five consecutive days in normal fowls, the
highest serum concentrations of josamycin achieved after
2 hours post each dose. The tissues concentrations follow-ing the last dose of repeated oral administrations were 7.52 ug/g in liver, 6.63 ug/g in fat, 5.90 ug/g in lung, 5.67 ug/g in kidney, 5.02 ug/g in gizzard, 2.57 ua/g in spleen, 1.61 ug/g in heart, 1.01 ug/g in breast muscles, 0.82 ug/g in thigh muscles after 24 hours from the last dose of repeated administrations. Also the drug persisted in lung tissues for 72 hours after administration and dis-appeared from all body tissues 96 hours of the last dose of repeated administrations. Following a single intramuscular administration of 18 mg/kg b.wt in normal fowls, josamycin reached its maximum concentration in serum, 0.5 h post-administration
with absorption half-life [t0.5(ab)] of 0.13 h. The elimi-nation half-life Et0.5(0] was 2.33 h. Following a single intravenous injection of 18 /kg b.wt in normal fowls previously aiven the sane dose of josamycin intramusc-ularlly, the drug obayed a two-compartments open model with half-life of distribution [t0.5(c()] was 0.16 h [V ] 1 [V2] and [Vdss] were 146.33, 203.91 and 350.23 ml/kg, respectively. [CLtot] was 0.93 ml/kg/min and the systemic bioavailability after intramuscular injection was 27.28%. During repeated intramuscular administrations josamycin (18 mg/kg b.wt) once daily for five consecutivedays in normal fowls revealed that the highest serum conce-ntrations occurred 0.5 hour after each dose. The tissues concentrations after the end of the last day of repeated intramuscular injections were 7.83 ug/g in liver, 4.87 ug/g in fat, 7.26 ug/g in lung, 6.06 ug/g in kidney, 4.55 ug/g in gizzard, 1.90 ug/g in spleen, 1.85 ug/g in heart, 2.35 ug/g in breast muscles, 3.20 ug/g in thigh muscles after 24 hours from the last dose of repeated administra-tions. Also the drug persisted in the lung tissues and fat for 72 hours after administration and disappeared from all body tissues 96 hours of the last dose of repeated adminis- trations.