Comparative biliary and serum kinetics of doxycycline after oral and intramuscular routes with special reference to its unique entero-hepatic circulation in turkeys

Citation:
Abo-EL-Sooud, K., G. A. Swielim, Y. R. Wally, and S. M. EL-Gammal, "Comparative biliary and serum kinetics of doxycycline after oral and intramuscular routes with special reference to its unique entero-hepatic circulation in turkeys", Wulfenia, 2016.

Abstract:

The present investigation was conducted to compare bile and serum concentrations of doxycycline
(DOX) in turkeys after single intramuscular (IM) and oral administrations of 20 mg/kg body weight (b.w.).
Furthermore, the entero-hepatic circulation and absolute bioavailability from gastrointestinal tract of DOX
after oral dose were accessed. Three groups of male turkeys of five each received DOX at a dose rate of 20
mg/kg b.w. intravenously, intramuscularly and orally. Samples of serum and bile excreted were taken at
predetermined intervals during 6 h. DOX concentrations of were determined by a reverse phase high-
performance liquid chromatography (HPLC) with UV detection at 347 nm. After intravenous (IV) injection
the elimination half-life (T1/2), the total body clearance (Cltot) and the volume of distribution (Vss) were
3.90 h, 0.55 L/h/kg and 2.39 L/kg, respectively. The maximal serum concentrations (Cmax) of DOX in
turkeys were 4.38 and 3.17 µg/ml, with time to peak concentration (Tmax) values of 0.74 and 1.00 h and
absolute bioavailability were 71.83 % and 48.81 %, after IM and oral administrations respectively. The bile
concentrations were up to 100 times higher than those in serum. The cumulative biliary excretion of the
administered dose DOX was about 7% and 3% recovered from the bile within the first 6 hr after IM and
oral dosing, respectively. After oral dose the entero-hepatic circulation model is based on the classical one
compartment model with bile elimination half-life (T1/2k1g) of 5.36 h and the maximal bile concentrations
(Cmax) was 222.39 µg/ml. Therefore DOX could be relevant for treatment of cholecyctitis and enteric
infectious diseases.

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