Pharmacokinetics and Effects of Alkalization after Intravenous Administration of Eltenac in Horses

Eltenac (ELT) [4-(2,6-dichlorophenyl)amino-3-thiophene] is a non-steroidal anti-inflammatory drug (NSAID) that was developed for veterinary use in horses and cattle. The pharmacokinetics of ELT was evaluated in horses at 0.5 mg/kg body weight (BW) after single IV injection after 5 days of repeated IV administration and after a single IV injection in horses previously subjected to 250 mg/kg BW of sodium bicarbonate (NaHCO3) as an alkalization treatment. The aim was to determine whether blood and subsequent urinary alkalization could modify the pharmacokinetics of ELT. Drug quantification was performed with serum and urine using high performance liquid chromatography with UV-visible detection. The results were also integrated with cyclo-oxygenase-inhibition literature data to review the dosage scheme of ELT in horses. After a single intravenous administration, ELT was characterized by rapid distribution (mean t1/2(lambda 1)= 0.18 +/- 0.07 hour) and a short elimination half-life (mean t1/2(lambda 2) = 2.9 +/- 0.68 hour). The volume of distribution was small (V-dss = 253.51 +/- 47.55 mL/kg), which is likely because of the high percentage of drug protein binding (approximately 97%). The AUC(0-infinity). and Cl-B were 6.92 +/- 0.84 h*mu g/mL and 73.2 +/- 10 mL/h/kg, respectively. Repeated administration did not cause either accumulation or modification of the pharmacokinetic profile. The in vitro effective concentrations were maintained for a 6-hour period. The alkalization procedure appeared to accelerate drug elimination, as ELT was quantifiable only for 6 hours; however, the drug clearance was not significantly modified. Thus, the administration of alkaline compounds to accelerate the elimination of ELT is not completely confirmed. (C) 2013 Elsevier Inc. All rights reserved.