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EC number: 221-967-7 | CAS number: 3296-90-0
Identification of14C Radioactivity in Liver and Bile
Liver homogenates from rats treated intravenously or orally with [14C] BMP (10mg/kg) were extracted into ethyl acetate in the presence of glycine/HCl buffer at 30 min(intravenous) and 40 min (oral) postdose and analysed by HPLC with radiometric detection.
The14C radioactivity in these liver extracts consisted of parent BMP and the glucuronide conjugate. After intravenous administration of [14C] BMP (150mg/kg) to BDC rats, more than 50% of the dose was excreted in the bile within 6 h (data not shown). HPLC- radiometric analysis showed greater than 99% of the BMP- derived14C equivalents excreted in bile over time consisted of a single peak, identified by chromatography as the glucuronide conjugate of BMP detected in urine (data not shown).
Pharmacikinetics of BMP and Identification of 14C Radioactivity in blood
Blood kinetics after a single intravenous administration of [14C] BMP (15mg/kg) indicated that parent BMP rapidly disappeared from the systemic circulation. The concentration- time profile of [14C] BMP in blood plasma after intravenous administration was best described in Fig. 5. After a rapid initial distribution of [14C] BMP, indicated by a short theoretical half-life of distribution (t½a; 3.4min), a significantly slower elimination (t½b; 2h) occurred. Blood plasma concentrations of BMP at times later than 30 min were very slow (1mg/ml).
[14C] BMP (10mg/kg) was administered orally and extracts obtained from small aliquots of whole blood (150ml per time point) and analyzed by LSC. The quantities of14C equivalents were close to or below the LOQ. Extracted BMP were quantifiable only at the first 4 time points (Fig.5). The area under the blood concentration- time curve for these 4 time points, compared with that after intravenous administration and adjusted for dose, suggests an oral bioavailability into the systemic circulation of less than 10%. The blood concentration- time profile after oral administration is presented for parent BMP at the quantifiable time points and for total [14C] BMP equivalents (Fig. 5.). After oral administration absorption was rapid with Cmax reached 40 min.14C equivalents were detected in the blood, although at very low levels, throughout to termination at 72h.
Hoehle et al. (2009) performed studies to characterize the dispositional and metabolic fate of Dibromoneopentyl glycol (BMP) after oral or intravenous administration to male F-344 rats. These studies report on the absorption, distribution, metabolism, and elimination of BMP and describe the pharmacokinetics of BMP. Additional studies were designed to determine whether repeated oral administration of BMP alters its disposition profile.
After a single oral administration of [14C]BMP (10 or 100 mg/kg) >80% of the low dose and 48% of the high dose were excreted by 12 h in the urine predominantly as a glucuronide metabolite. After repeated daily oral doses for 5 or 10 days, route and rate of elimination were similar to those obtained after single administrations of BMP. In all studies, the radioactivity recovered in feces was low (<15%). The total amt. of radioactivity remaining in tissues at 72 h after a single oral administration of BMP (100 mg/kg) was less than 1% of the dose, and repeated daily dosing did not lead to retention in tissues. After i.v. administration, the radiolabeled test material was found in blood decreased rapidly. Excretion profiles were similar to those after oral administration. Parent BMP and BMP glucuronide were present in blood plasma after oral or i.v. dosing. After an i.v. dose of BMP (15 mg/kg) the hepatic BMP glucuronide was primarily exported into the bile (>50% within 6 h), but it underwent enterohepatic recycling with subsequent elimination in the urine. These data indicate that the extensive excretion and rapid glucuronidation by the liver limits exposure of internal tissues to BMP by greatly reducing its systemic bioavailability after oral exposure.
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