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

• Verfasst von: Kropp, Joachim [VerfasserIn]
• Verfasst von: Eisenhut, Michael [VerfasserIn]
• Titel: Pharmacokinetics and metabolism of the methyl-branched fatty acid (BMIPP) in animals and humans
• Verf.angabe: Joachim Kropp, Michael Eisenhut, Kathleen R. Ambrose, Furn F. (Russ) Knapp and Wolf-Gunter Franke
• Jahr: 1999
• Umfang: 8 S.
• Fussnoten: Gesehen am 09.02.2021
• Titel Quelle: Enthalten in: Journal of nuclear medicine
• Ort Quelle: New York, NY : Soc., 1964
• Jahr Quelle: 1999
• Band/Heft Quelle: 40(1999), 9, Seite 1484-1491
• ISSN Quelle: 2159-662X
• ISSN Quelle: 1535-5667
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 174789916X

Abstract

<p>The aim of this study was to further characterize the major metabolite of 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP). <b>Methods:</b> Radioactive components of ¹³¹I-BMIPP were evaluated in Langendorff-perfused rat hearts, as well as in blood samples from 20 patients after injection of ¹²³I-BMIPP. Rat hearts were perfused with pH 7.4 Krebs-Henseleit buffer with or without 0.4 mmoI/L bovine serum albumin (BSA) or 0.4 mmoI/L palmitate. Lipids were Folch extracted and hydrolyzed from samples of the outflow, as well as from homogenized hearts. Radioactive components were determined by thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analyses. The major metabolite of BMIPP was then further characterized by electrospray mass spectrometry. <b>Results:</b> 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 perfusate buffer significantly increased back diffusion of BMIPP (R^f = 0.55), as well as reduced BMIPP uptake and metabolism. The major metabolite was identified by mass spectral analysis as 2-(piodophenyl) acetic acid (IPC₂). From TLC and HPLC analyses of the serum lipids obtained from patients, the same metabolite could be identified with levels increasing overtime (0%, 5.2% and 11.8% of the injected dose; 3 min, 20 min and 3 h postinjection, respectively). In addition to the identification of unmetabolized BMIPP (53.9%), the rat heart lipid hydrolysate also contained α-methyl-14-(p-iodophenyl)tet radecanoic acid (20.8%), 12-(p-iodophenyl)-substituted-dodecanoic (17.1%), -hexanoic acid (5.2%) and IPC₂ (1.1%). <b>Conclusion:</b> The animal results show the complexity of uptake, metabolism and release of BMIPP from which a part is metabolized through α- and subsequent ß-oxidation to the final IPC₂ metabolite as confirmed by mass spectral analysis. The results from patient studies suggest that the slow myocardial washout observed in vivo after intravenous administration of BMIPP may represent a similar process, because both unmetabolized BMIPP and the final metabolite were also identified in serum samples.</p>