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Influence of age, frailty and liver function on the pharmacokinetics of brofaromine
The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y). Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from...
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| Published in: | European journal of clinical pharmacology 1996, Vol.49 (5), p.387-391 |
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| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
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| container_end_page | 391 |
| container_issue | 5 |
| container_start_page | 387 |
| container_title | European journal of clinical pharmacology |
| container_volume | 49 |
| creator | ZEEH, J FUCHS, L BERGMANN, W ANTONIN, K.-H DEGEL, F BIECK, P PLATT, D |
| description | The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y).
Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance).
In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001).
Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance. |
| doi_str_mv | 10.1007/BF00203783 |
| format | article |
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Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance).
In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001).
Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.</description><identifier>ISSN: 0031-6970</identifier><identifier>EISSN: 1432-1041</identifier><identifier>DOI: 10.1007/BF00203783</identifier><identifier>PMID: 8866634</identifier><language>eng</language><publisher>Heidelberg: Springer</publisher><subject>Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Aging - metabolism ; Aging - pathology ; Biological and medical sciences ; Caffeine - blood ; Chromatography, Gas ; Cross-Over Studies ; Cytochrome P-450 CYP1A2 - metabolism ; Female ; Frail Elderly ; Half-Life ; Humans ; Liver Function Tests ; Male ; Medical sciences ; Monoamine Oxidase Inhibitors - administration & dosage ; Monoamine Oxidase Inhibitors - blood ; Monoamine Oxidase Inhibitors - pharmacokinetics ; Neuropharmacology ; Pharmacology. Drug treatments ; Piperidines - administration & dosage ; Piperidines - blood ; Piperidines - pharmacokinetics ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Regression Analysis ; Sorbitol - blood</subject><ispartof>European journal of clinical pharmacology, 1996, Vol.49 (5), p.387-391</ispartof><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c226t-66294b19719f2623c3acd89a64a0f27ea363cc9f240f749a4bc1633bb186d2c03</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2980388$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8866634$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZEEH, J</creatorcontrib><creatorcontrib>FUCHS, L</creatorcontrib><creatorcontrib>BERGMANN, W</creatorcontrib><creatorcontrib>ANTONIN, K.-H</creatorcontrib><creatorcontrib>DEGEL, F</creatorcontrib><creatorcontrib>BIECK, P</creatorcontrib><creatorcontrib>PLATT, D</creatorcontrib><title>Influence of age, frailty and liver function on the pharmacokinetics of brofaromine</title><title>European journal of clinical pharmacology</title><addtitle>Eur J Clin Pharmacol</addtitle><description>The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y).
Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance).
In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001).
Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - metabolism</subject><subject>Aging - pathology</subject><subject>Biological and medical sciences</subject><subject>Caffeine - blood</subject><subject>Chromatography, Gas</subject><subject>Cross-Over Studies</subject><subject>Cytochrome P-450 CYP1A2 - metabolism</subject><subject>Female</subject><subject>Frail Elderly</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Liver Function Tests</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Monoamine Oxidase Inhibitors - administration & dosage</subject><subject>Monoamine Oxidase Inhibitors - blood</subject><subject>Monoamine Oxidase Inhibitors - pharmacokinetics</subject><subject>Neuropharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Piperidines - administration & dosage</subject><subject>Piperidines - blood</subject><subject>Piperidines - pharmacokinetics</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. 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Drug treatments</topic><topic>Piperidines - administration & dosage</topic><topic>Piperidines - blood</topic><topic>Piperidines - pharmacokinetics</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Regression Analysis</topic><topic>Sorbitol - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZEEH, J</creatorcontrib><creatorcontrib>FUCHS, L</creatorcontrib><creatorcontrib>BERGMANN, W</creatorcontrib><creatorcontrib>ANTONIN, K.-H</creatorcontrib><creatorcontrib>DEGEL, F</creatorcontrib><creatorcontrib>BIECK, P</creatorcontrib><creatorcontrib>PLATT, D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZEEH, J</au><au>FUCHS, L</au><au>BERGMANN, W</au><au>ANTONIN, K.-H</au><au>DEGEL, F</au><au>BIECK, P</au><au>PLATT, D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of age, frailty and liver function on the pharmacokinetics of brofaromine</atitle><jtitle>European journal of clinical pharmacology</jtitle><addtitle>Eur J Clin Pharmacol</addtitle><date>1996</date><risdate>1996</risdate><volume>49</volume><issue>5</issue><spage>387</spage><epage>391</epage><pages>387-391</pages><issn>0031-6970</issn><eissn>1432-1041</eissn><abstract>The pharmacokinetics of brofaromine, a selective inhibitor of monoamine oxidase A, was evaluated in 12 frail elderly patients (66-92 y) and 12 healthy volunteers (20-35 y).
Quantitative liver function tests were performed to show whether brofaromine elimination in the elderly could be predicted from noninvasive assessment of CYP1A2 activity (caffeine clearance) or liver plasma flow (sorbitol clearance).
In the elderly the AUC of brofaromine was significantly increased (e.g. for the 75 mg dose 43.2 vs 19.9 mumol*h.l-1, clearance was reduced (5.0 vs. 11.8 l.h-1), the volume of distribution was smaller (130 vs. 230 l), and the half-life was slightly increased (19.0 vs. 14.2 h). No significant correlation was observed between hepatic plasma flow and brofaromine clearance (r = 0.41, P = 0.05), whereas CYP1A2 activity and brofaromine clearance were tightly correlated (r = 0.94, P < 0.0001).
Caffeine clearance, a simple, noninvasive test of CYP1A2 activity, is predictive of brofaromine clearance.</abstract><cop>Heidelberg</cop><cop>Berlin</cop><pub>Springer</pub><pmid>8866634</pmid><doi>10.1007/BF00203783</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | European journal of clinical pharmacology, 1996, Vol.49 (5), p.387-391 |
| issn | 0031-6970 1432-1041 |
| language | eng |
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| source | Springer Online Journal Archives |
| subjects | Administration, Oral Adult Aged Aged, 80 and over Aging - metabolism Aging - pathology Biological and medical sciences Caffeine - blood Chromatography, Gas Cross-Over Studies Cytochrome P-450 CYP1A2 - metabolism Female Frail Elderly Half-Life Humans Liver Function Tests Male Medical sciences Monoamine Oxidase Inhibitors - administration & dosage Monoamine Oxidase Inhibitors - blood Monoamine Oxidase Inhibitors - pharmacokinetics Neuropharmacology Pharmacology. Drug treatments Piperidines - administration & dosage Piperidines - blood Piperidines - pharmacokinetics Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Regression Analysis Sorbitol - blood |
| title | Influence of age, frailty and liver function on the pharmacokinetics of brofaromine |
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