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

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  • AMA.S.J.P.A.M. VAN Miert
    A.S.J.P.A.M. VAN Miert
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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 (IMP) 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, bioavail‐ability, volume of distribution) were determined both for TMP and SCP. Following intravenous administration, the volume of distribution at steady‐state (Vd(33)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. Based on the pharmacokinetic data obtained and the publishedin vitrosensitivity data, it may be predicted that TMP and SCP given intravenously or by nasogastric tube at a dose of 5 mg/kg and 25 mg/kg respectively and a dosage interval of 8–12 h would result in sufficiently high plasma concentrations for effectiveness against susceptible bacteria. The single oral administration of TMP and SCP mixed with concentrate did not result in effective plasma concentrations. Further studies are needed to investigate whether higher plasma concentrations would be achieved by a multiple dosing scheme for several days.

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