Pharmacokinetics and metabolism of the methyl-branched fatty acid (BMIPP) in animals and humans

The aim of this study was to further characterize the major metabolite of 1 5-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP). Methods: Radioac tive components of I-131-BMIPP were evaluated in Langendorff-perfused rat h earts, as well as in blood samples from 20 patients after injection of I-12 3-BMIPP. Rat hearts were perfused with pH 7.4 Krebs-Henseleit buffer with o r without 0.4 mmol/L bovine serum albumin (BSA) or 0.4 mmol/L palmitate. Li pids were Folch extracted and hydrolyzed from samples of the outflow, as we ll as from homogenized hearts. Radioactive components were determined by th in-layer chromatography (TLC) and high-performance liquid chromatography (H PLC) analyses. The major metabolite of BMIPP was then further characterized by electrospray mass spectrometry. Results: The rat heart perfusate showed one major polar metabolite observed by TLC (R-f = 0.35; solvent = benzene- dioxane-acetic acid 80:18:2). The addition of BSA/palmitate to the perfusat e buffer significantly increased backdiffusion of BMIPP (R-f = 0.55), as we ll as reduced BMIPP uptake and metabolism. The major metabolite was identif ied by mass spectral analysis as 2-(p-iodophenyl)acetic acid (IPC2). From T LC and HPLC analyses of the serum lipids obtained from patients, the same m etabolite could be identified with levels increasing over time (0%, 5.2% an d 11.8% of the injected dose; 3 min, 20 min and 3 h postinjection, respecti vely). In addition to the identification of unmetabolized BMIPP (53.9%), th e rat heart lipid hydrolysate also contained alpha-methyl-14-(p-iodophenyl) tetradecanoic acid (20.8%), 12-(p-iodophenyl)-substituted-dodecanoic (17.1% ), -hexanoic acid (5.2%) and IPC2 (1.1%). Conclusion: The animal results sh ow the complexity of uptake, metabolism and release of BMIPP from which a p art is metabolized through alpha- and subsequent beta-oxidation to the fina l IPC2 metabolite as confirmed by mass spectral analysis. The results from patient studies suggest that the slow myocardial washout observed in vivo a fter intravenous administration of BMIPP may represent a similar process, b ecause both unmetabolized BMIPP and the final metabolite were also identifi ed in serum samples.