| An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy. | |
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MedLine Citation:
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PMID: 7910120 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Therapy with racemic compounds produces effects that can be attributed to both (S)- and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while the enantiomers of propafenone exert similar sodium channel-blocking (QRS widening) effects, it is the (S)-enantiomer that produces beta-blockade; moreover, we have demonstrated recently that (R)-propafenone inhibits the metabolism of (S)-propafenone in vitro. METHODS AND RESULTS: This single-blind, randomized study compared the effects of (R/S)-, (S)-, (R)-propafenone (150 mg q 6 hours for 4 days) and placebo on QRS duration (delta QRS) and on maximum exercise heart rate (delta HRmax), an index of beta-blockade. The clearance of (S)-propafenone was significantly lower (-55 +/- 24%, P < .001) during treatment with (R/S)-propafenone than with the (S)-enantiomer alone, and delta HRmax was significantly altered during (R/S)-propafenone (-8.8 +/- 6.6 beats per minute; P < .01) and during (S)-propafenone (-4.3 +/- 4.8 beats per minute; P < .01) but not during (R)-propafenone (-1.8 +/- 6.4 beats per minute) or placebo (0.3 +/- 7.1 beats per minute). In contrast, (R/S)-, (S)-, and (R)-propafenone all prolonged QRS compared with placebo. CONCLUSIONS: These data indicate that (R)-propafenone impairs the disposition of (S)-propafenone in humans. As a result, the beta-blocking effects of 150 mg of racemic propafenone (75 mg of the [S]-enantiomer) were more pronounced than those of 150 mg of (S)-propafenone alone. Thus, the effects of racemic drug therapy are not necessarily those predicted by summation of the effects of the individual enantiomers. |
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Authors:
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H K Kroemer; M F Fromm; K Bühl; H Terefe; G Blaschke; M Eichelbaum |
Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 89 ISSN: 0009-7322 ISO Abbreviation: Circulation Publication Date: 1994 May |
Date Detail:
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Created Date: 1994-06-14 Completed Date: 1994-06-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2396-400 Citation Subset: AIM; IM |
Affiliation:
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Dr Margarete Fischer-Bosch-Institut für Klinische, Pharmakologie, Stuttgart, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Antagonists
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chemistry,
pharmacokinetics*,
pharmacology* Adult Electrocardiography Humans Male Propafenone / chemistry, pharmacokinetics*, pharmacology* Receptors, Adrenergic, beta / drug effects* Single-Blind Method Sodium Channels / drug effects Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Receptors, Adrenergic, beta; 0/Sodium Channels; 54063-53-5/Propafenone |
| Comments/Corrections | |
Comment In:
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Circulation. 1994 May;89(5):2451-3
[PMID:
7910122
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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