Pharmacokinetics of Mequindox and Its Metabolites in Swine

The present study was carried out to investigate the pharmacokinetics of mequindox （MEQ）, a new synthetic quinoxaline 1,4-dioxide derivative and its two main metabolites M1 [2-isoethanol mequinoox], M2 [2-isoethanol 1-desoxymequindox] in healthy swine. MEQ （10 mg kg-1 body weight） was administered to nine healthy cross-bread swine via oral, intramuscular, and intravenous routes in a randomized 3x3 crossover design with a 1-wk washout period. A sensitive high-performance liquid chromatography （HPLC） method was used for the determination of plasma concentrations of MEQ and its metabolites M1 and M2. Plasma concentration versus time profiles of MEQ and its metabolites, M1 and M2, were analyzed by noncompartmental analysis using WinNonlin 5.2 software. The mean maximum concentrations （Cmax） of M1 and M2 after intravenous administration of MEQ were （5.27±1.59） lag mL-1 at 1.78 h and （1.01±0.29） μg mL-1 at 0.92 h, respectively. The mean maximum concentrations （Cmax） ofMEQ, M1, and M2 were found to be （6.96±3.23）, （6.61±1.56）, and （0.78 ±0.25） lag mL-1 respectively at 0.15, 1.61, and 1.30 h after intramuscular administration of MEQ, respectively and （0.75±0.45）, （6.90±1.52）, and （0.62±0.21） lag mL-1, respectively at 0.40, 1.57, and 2.00 h, respectively after oral administration of MEQ. The apparent elimination half-lives （b2） ofMEQ, M1, and M2 were （0.84±0.35）, （7.57±3.93）, and （9.56±6.00） h, respectively after intravenous administration of MEQ; （0.50±0.25）, （6.30±3.00）, and （5.94±2.54） h, respectively after intramuscular administration of MEQ; and （1.64± 1.17）, （5.59±1.93）, and （16.25±10.27） h, respectively after oral administration of MEQ. The mean areas under the plasma concentration-time curve （AUC0-∝） of MEQ, M1, and M2 were （4.88±1.54）, （36.93±17.50）, and （5.16±94） μg h mL-1, respectively after intravenous administration of MEQ; （4.18±0.76）, （48.25±20.82）, and （4.88±2.21） μg h mL-1 , respectively after intramuscular administration of MEQ; and （1.01±0.40）, （48.83±20.71）, and （5.54±2.23） μg h mL-1, respectively after oral administration of MEQ. MEQ was rapidly absorbed and metabolized in swine after oral, intramuscular, and intravenous administration. Further studies are required to investigate the double-peak phenomenon observed in the plasma concentration-time profile after oral administration and the pharmacokinetics of other metabolites of MEQ.

Pharmacokinetics of Quinocetone and Its Major Metabolites in Swine After Intravenous and Oral Administration

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1 body weight respectively in a randomized crossover design test with two-week washout period.A sensitive high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method was developed for the determination of quinocetone and its metabolite 1-desoxyquinocetone in plasma.Plasma concentration versus time profiles of quinocetone and its metabolite 1-desoxyquinocetone were analyzed by non-compartmental analysis using Winnonlin 5.2 software.Mean maximum concentrations （Cmax） for quinocetone was found to be （0.56±0.13） μg mL-1 at 2.92 h,after oral administration of quinocetone.Mean maximum concentrations （Cmax） for 1-desoxyquinocetone after intravenous or oral administration of quinocetone were （0.0095±0.0012） μg mL-1 at 0.083 h and （0.0067±0.0053） μg mL-1 at 3.08 h.The apparent elimination half-lives （T1/2） for quinocetone and its metabolite 1-desoxyquinocetone were （2.24±0.24） and （5.23±0.56） h after intravenous administration of quinocetone and （2.91±0.29） and （11.85±2.89） h after oral administration of quinocetone,respectively.Mean areas under the plasma concentration-time curve （AUC0-∞） for quinocetone and 1-desoxyquinocetone were （2.02±0.15） and （0.2±0.002） μg h mL-1 respectively after intravenous administration of quinocetone,and （3.5±0.79） and （0.053±0.03） μg h mL-1 after oral administration of quinocetone,respectively.Quinocetone was rapidly absorbed and metabolized in swine after oral and intravenous administration.The plasma concentration-time curve （AUC0-∞） of 1-desoxyquinocetone were much smaller than those of quinocetone,while the elimination half-lives （T1/2） were much longer than those of quinocetone after intravenously （i.v.） or oral administration.