Pharmacokinetics and bioavailability of doxycycline in turkeys

Abstract

The pharmacokinetic parameters of doxycycline (DOX) were determined in 3 day, 3-, 6- and 12-week-old fasted turkeys, after a single intravenous (i.v.) dose of 25 mg doxycycline. HCl/kg body weight. Doxycycline disposition fitted an open two-compartment model. The mean (+/-SD) elimination half-life was 10.6 +/- 0.7, 10.8 +/- 1.5, 7.9 +/- 1.4 and 10.0 +/- 0.9 h in 3 day, 3-, 6- and 12-week-old turkeys, respectively. Mean (+/- SD) total body clearance was 0.19 (+/-0.01), 0.27 (+/-0.03), 0.11 (+/-0.03) and 0.06 (+/-0.01) L/h.kg in 3 day, 3-, 6- and 12-week-old turkeys, respectively. The steady-state volume of distribution was 1.77 (+/-0.2), 2.1 (+/-0.2), 0.7 (+/-0.4) and 0.5 (+/-0.2) L/kg in turkeys of the above mentioned ages, respectively. The AUC value significantly increased with the age of the turkeys. An oral doxycycline solution at a single dose of 25 mg/kg of body weight was administered to 3 day. 3-, 6- and 12-week-old turkeys. The maximal plasma concentrations in fasted turkeys were 3.8, 5.6, 7.4 and 5.7 micrograms/mL. with tmax values of 4.7, 1.5, 2.8 and 5.4 h, for the different ages, respectively. In fed turkeys the Cmax values were 2.5, 6.1, 4.8 and 3.0 micrograms/mL. with tmax values of 4.2, 5.3, 4.5 and 7.5 h, respectively. The absolute bioavailability in fasted turkeys varied between 25.0 +/- 9.0% (for 12-week-old birds) and 63.5 +/- 7.1% (for 3-week-old birds). The relative bioavailability varied between 40.0 +/- 13.0% (for 12-week-old birds) and 83.7 +/- 14.3% (for 3-week-old birds).

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

“…The discrepancies between values calculated for pharmacokinetic parameters may be attributed to the animal species, the drug formulation employed, the age, size or sex of the animals, to differences in fatty tissue deposits between animal species or breeds, or even to inter-individual variations (Riond et al, 1989;Jha et al, 1989). Doxycycline pharmacokinetics after PO administration were best described in this animal species by a 2-compartment open model, which is in accordance with previous studies in pigs (Baert et al, 2000), calves with immature ruminal function (van Gool et al, 1986;Meijer et al, 1993), chickens (Anadó n et al, 1994;Espigol et al, 1997;Laczay et al, 2001) and turkeys (Santos et al, 1996).…”

“…As expected in ruminants, the results of our study indicate that doxycycline is partially absorbed when administered orally. Meijer et al (1993) reported higher bioavailability values in calves with immature ruminal function (69 ± 12%), but most previous studies observed an absorption value similar to ours, including studies performed in chickens (41.3 ± 2%) (Anadó n et al, 1994), turkeys (25-64%) (Santos et al, 1996), and pigs (21.2 ± 7.5%) (Baert et al, 2000). Although the loss of doxycycline in the forestomachs may play an important role, these discrepancies are in accordance with those reported for other tetracyclines, and are related to the animal species studied (Nielsen and GyrdHansen, 1996), the pharmacokinetic curve-fitting routines or the analytical techniques used (Meijer et al, 1993), the drug formulation administered, and the health status of the animals (Abd El-Aty et al, 2004).…”

“…In turkeys, however, t max was considerably higher (7.5 ± 4.3 h), possibly due to doxycycline adsorption to the intestinal wall or food particles, or to a slower absorption process in this avian species (Santos et al, 1996).…”

“…Doxycycline pharmacokinetics have been studied in several animal species (Wilson et al, 1988;Jha et al, 1989;Riond et al, 1989;Greth et al, 1993;Meijer et al, 1993;Santos et al, 1996;Baert et al, 2000;Laczay et al, 2001;Abd El-Aty et al, 2004;Davis et al, 2006) and in man (Schach von Wittenau and Chiaini, 1968;Raghuram and Krishnaswamy, 1982;Riond and Riviere, 1988), but few studies have been done in sheep (Ziv and Sulman, 1974).…”

“…The pharmacokinetics of doxycycline have been fully documented in humans (Schach von Wittenau and Chiaini, 1968;Raghuram and Krishnaswamy, 1982;Riond and Riviere, 1988) and, to a lesser extent, in veterinary species, such as dogs (Wilson et al, 1988;, cats , pigs Baert et al, 2000), horses (Davis et al, 2006), and poultry (Anadó n et al, 1994;Santos et al, 1996;Laczay et al, 2001). Limited information is available on the pharmacokinetics of doxycycline in ruminant species, where it has been studied in calves in mature and immature ruminal function (Riond et al, 1989;Meijer et al, 1993) and in goats (Jha et al, 1989;Abd El-Aty et al, 2004), but to date no studies have been conducted in sheep.…”