Pharmacokinetics of trimethoprim/sulphachlorpyridazine in horses after oral, nasogastric and intravenous administration

Abstract

In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bioavailability, volume of distribution) were determined both for TMP and SCP. Following intravenous administration, the volume of distribution at steady-state (Vd(ss)) was significantly larger for TMP (1.51 +/- 0.25 L/kg than for SCP (0.26 +/- 0.05 L/kg. The clearance was 7.73 +/- 2.26 mL/min.kg for TMP and 2.64 +/- 0.48 mL/min.kg for SCP. For both TMP and SCP, mean peak plasma concentrations (Cmax) and the bioavailabilities (F) were reduced significantly when the drugs were mixed with concentrate (ct) as compared with those after nasogastric administration (ngt) (Fct = 44.3 +/- 10.7% vs. Fngt = 68.3 +/- 12.5% for TMP; Fct = 46.3 +/- 8.9% vs. Fngt = 67.3 +/- 13.7% for SCP). Following the administration of TMP and SCP mixed with concentrate, the plasma concentration-time curves showed a biphasic absorption pattern in all horses. The first peak occurred 1-2 h and the second peak 8-10 h after administration of the combination preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of orally administered trimethoprim and sulfadiazine into noninfected subcutaneous tissue chambers in adult ponies

“…The great variation in T max between individual ponies found in the present study (range 1–9 h) has also been found by others (van Duijkeren et al ., 1995; Gustafsson et al ., 1999). The bi‐phasic absorption seen in two ponies has been described earlier for a TMP/sulfachlorpyridazine combination in horses fed concentrates (van Duijkeren et al ., 1995) and for phenylbutazone in ponies fed hay (Maitho et al ., 1986). When horses were fasted 12 h before TMPS administration no double peaks were obtained (van Duijkeren et al ., 1994b).…”

“…Trimethoprim–sulfonamide (TMPS) combinations are used extensively in equine practice because of their broad spectrum of activity against many Gram‐positive and Gram‐negative bacteria and their clinical efficacy (van Duijkeren et al ., 1994a). Moreover, TMPS combinations have a relatively high bioavailability following oral administration (van Duijkeren et al ., 1994b; van Duijkeren et al ., 1995) with only minor effects on the equine intestinal flora (Ensink et al ., 1996b; Gustafsson et al ., 1999). Generally, effective antimicrobial therapy should produce and maintain effective concentrations of the drug at the site of infection for a sufficient period of time to kill or inhibit bacteria without toxic effects to the host (Prescott & Baggot, 1993).…”

Evaluation of an oral direct factor Xa inhibitor anticoagulant in healthy adult horses

“…In the present study, the DiXa drug was given carefully by mouth and not by nasogastric tube. It should be considered that this type of drug administration may lead to an unknown amount of drug loss at the moment of oral administration . However, the authors consider this possibility unlikely given that great care was used during oral administration of the DiXa drug and at no time did horses drop the mixture of drug with honey.…”

Antimicrobial disposition in pulmonary epithelial lining fluid of horses. Part I. Sulfadiazine and trimethoprim

“…SDZ/TMP ratios in equine plasma have been studied after intravenous and oral administration (Van Duijkeren et al. , 1994a; Van Duijkeren et al. , 1995b), and the 20:1 ratio in plasma was approached up to 6 h after intravenous administration and approximately up to 9 h after repeated oral administrations.…”