Pharmacokinetic data on doxycycline and its distribution in different biological fluids in female goats

Abstract

A pharmacokinetic study of doxycycline after intravenous administration at 5 mg/kg body weight in goats revealed that a concentration of greater than or equal to 0.5 microgram/ml was maintained for 5 min-2 h, 4-12 h, 2-12 h and 5 min-greater than 48 h in plasma, interstitial fluid, milk and urine respectively. The low t1/2 alpha of 0.73 +/- 0.11 h and high t1/2 beta of 16.63 +/- 1.58 h show that the drug is rapidly distributed but slowly eliminated from the body. The tissue:plasma concentration of 4.86 +/- 1.06 during the elimination phase [K12/(K21-beta)] indicates a high expected tissue concentration, which is supported by similarly increased drug concentration in interstitial fluid and milk. The high Vdarea of 9.78 +/- 0.86 L/kg observed denotes that, apart from its wide distribution, the drug may be stored in fat depots as it is known to be highly lipophilic. As the drug maintained a therapeutic concentration for a shorter time in plasma, and the calculated dose rate for maintaining a minimal plasma concentration of 0.5-1.5 micrograms/ml is relatively high, it may not be of much use in treating septicaemia in this species. Since the observed tissue:plasma concentration was higher and a therapeutic concentration was maintained in interstitial fluid and milk for longer, the drug can be used for other systemic infections at a lower dose rate than that required for treating septicaemia. As the drug maintained a very high concentration in urine, it may be of particular value in treating urinary tract infections caused by sensitive micro-organisms.

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

“…Other authors have reported values of the volume determined by the area method (V a ). In our study, V a was clearly lower than values obtained by Abd El-Aty et al (2004) in goats (6.48 ± 0.12 L/kg) and by Jha et al (1989) in lactating goats (9.78 ± 0.86 L/kg).…”

“…Our values were lower than those calculated in goats with mature ruminal function (11.83 ± 0.67 mL/kg/min) (Abd El-Aty et al, 2004). 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).…”

“…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).…”

“…This drug is highly lipophilic, and would be expected to exhibit extensive tissue distribution, probably with tissue binding and/or intracellular penetration (Riond et al, 1989). Jha et al (1989) and Abd El-Aty et al (2004) suggested that doxycycline could be accumulated in fat. Our values are similar to those previously reported in calves with immature (1.81 ± 0.24 L/ kg) or mature (1.31 ± 0.11 L/kg) ruminal function (Riond et al, 1989), and higher than those reported in non-ruminant species such as cats (0.34 ± 0.03 L/kg) , dogs (0.93 ± 0.14 L/kg) , and pigs (0.53 ± 0.04 L/kg, and 0.89 ± 0.16 L/kg) Baert et al, 2000, respectively).…”

“…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. Ziv and Sulman (1974) briefly described the intravenous (IV) kinetics of this drug in sheep, although data were reported as a mean of values obtained from the two animal species used in the study, namely cows and sheep.…”