ABSORPTION, METABOLISM, AND EXCRETION OF 2,3 4,5-BIS(2-BUTYLENE) TETRAHYDRO-2 FURALDEHYDE (MGK R11) IN THE RAT/

Experiments were conducted in four groups of rats to determine the abs orption, distribution, metabolism, and excretion (ADME) patterns follo wing oral administration of [formyl-C-14] 2,3:4,5-bis(2-butylene) tetr ahydro-2 furaldehyde (MGK R11). Ten rats (five males and five females) were used in each of the four experiments. Fasted rats were administe red [formyl-C-14] MGK R11 at a single oral dosage of 65 mg/kg, at a si ngle oral dosage of 1000 mg/kg, and at a daily oral dosage of 65 mg/kg of nonradiolabeled compound for 14 days followed by a single dose of C-14-labeled compound at 65 mg/kg. Rat blood kinetics were determined in the fourth group following a single oral dose of 65 mg/ kg. Each an imal was administered approximately 12-14 mu Ci of radioactivity. Urin e and feces were collected from all groups at predetermined time inter vals. Seven days after dose administration, the rats were euthanized a nd selected tissues and organs were harvested. Samples of urine, feces , and tissues were subsequently analyzed for C-14 content. In the bloo d kinetics study, radioactivity peaked at approximately 30 min in both the males and females, indicating very rapid absorption. The decline of radioactivity from blood followed a biphasic elimination pattern. T he first half-life was 1.36 h for males and 1.18 h for females. In the second phase, the half-life was 21 h for males and 26 h for females. Female rats excreted 67.21-86.85% of the radioactivity in urine and 13 .99-28.08% in feces, whereas male rats excreted 50.19-64.37% of the ad ministered radioactivity in urine and 31.43-40.94% in feces. Tissue re sidues of C-14 ranged between 0.47% and 1.09% of the administered dose . The total mean recovered radioactivity of the administered dose in t he four definitive studies ranged between 92% and 101%, No parent comp ound was detected in the urine. Three major and one minor metabolite w as isolated by highperformance liquid chromatography (HPLC) and identi fied by gas chromatography/mass spectrometry (GC/MS). One major metabo lite was formed by oxidation of the aldehyde moiety to the carboxylic acid. A second metabolite was the glucuronic acid conjugate of the car boxylic acid and the third was formed by reduction of the aldehyde moi ety of MGK R11 to an alcohol followed by glucuronic acid conjugation. The minor metabolite was the unconjugated alcohol derivative of MGK R1 1. The gender of the animals affected the rate, route of excretion, an d metabolic profile. The urinary excretion rate was faster in females than in males and the amount excreted was also greater in female rats.