Pharmacokinetics and metabolism of the methyl-branched fatty acid (BMIPP) in animals and humans
<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 <sup>131</sup>I-BMIPP were evaluated in Langendorff-perfused rat hearts, as well as in bloo...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
1999
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| In: |
Journal of nuclear medicine
Year: 1999, Volume: 40, Issue: 9, Pages: 1484-1491 |
| ISSN: | 2159-662X |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://jnm.snmjournals.org/content/40/9/1484
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| Author Notes: | Joachim Kropp, Michael Eisenhut, Kathleen R. Ambrose, Furn F. (Russ) Knapp and Wolf-Gunter Franke |
| Summary: | <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 <sup>131</sup>I-BMIPP were evaluated in Langendorff-perfused rat hearts, as well as in blood samples from 20 patients after injection of <sup>123</sup>I-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<sub>f</sub> = 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<sup>f</sup> = 0.55), as well as reduced BMIPP uptake and metabolism. The major metabolite was identified by mass spectral analysis as 2-(piodophenyl) acetic acid (IPC<sub>2</sub>). 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 IPC<sub>2</sub> (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 IPC<sub>2</sub> 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> |
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| Item Description: | Gesehen am 09.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 2159-662X |