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Drug Metabolism & Disposition

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Rapid CommunicationShort Communication

Chronic Nifedipine Dosing Enhances Cephalexin Bioavailability and Intestinal Absorption in Conscious Rats

F. Berlioz, B. Lepére-Prevot, S. Julien, A. Tsocas, C. Carbon, C. Rozé and R. Farinotti
Drug Metabolism and Disposition November 2000, 28 (11) 1267-1269;
F. Berlioz
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B. Lepére-Prevot
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S. Julien
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A. Tsocas
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C. Carbon
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C. Rozé
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R. Farinotti
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Abstract

Cephalexin, a β-lactam antibiotic, is rapidly absorbed via the di-and tripeptide intestinal transporters, as for many peptidomimetic drugs. Acute nifedipine has been shown to increase intestinal absorption of several β-lactams: amoxicillin and cefixime in humans, and cephalexin in the rat. We showed previously that the nervous system was involved in the increasing effect of nifedipine on cephalexin intestinal absorption in anesthetized rats. The aim of the present study was 2-fold: 1) to investigate whether the effect of nifedipine is maintained in conscious rats, and 2) to determine whether the nifedipine effect will persist during chronic nifedipine administration. Acute and chronic oral administration of nifedipine significantly increased oral cephalexin area under the plasma concentration-time curve (34 and 25%, respectively) and maximum concentration in plasma (57 and 51%, respectively), while the distribution and elimination parameters of intra-arterial cephalexin were not affected by acute or chronic nifedipine administration. In conclusion, acute nifedipine effect on intestinal absorption of cephalexin is independent of anesthesia in rats. Since nifedipine could still enhance cephalexin intestinal absorption after a 7-day b.i.d. treatment, it can be envisaged to apply this effect to increase bioavailability of poorly absorbed peptidomimetic drugs in man.

Footnotes

  • Send reprint requests to: Pr. R. Farinotti, UPRES 2706, Faculté de Pharmacie, 5 rue J. B. Clément, 92290 Chatenay-Malabry Cedex, France. E-mail:robert.farinotti{at}bch.ap-hop-paris.fr

  • Abbreviations used are::
    CFX
    cephalexin
    i.a.
    intra-arterial
    KRB
    Krebs-Ringer buffer solution
    AUC
    area under the plasma concentration-time curve
    NFP
    nifedipine
    • Received October 27, 1999.
    • Accepted July 26, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 28 (11)
Drug Metabolism and Disposition
Vol. 28, Issue 11
1 Nov 2000
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Rapid CommunicationShort Communication

Chronic Nifedipine Dosing Enhances Cephalexin Bioavailability and Intestinal Absorption in Conscious Rats

F. Berlioz, B. Lepére-Prevot, S. Julien, A. Tsocas, C. Carbon, C. Rozé and R. Farinotti
Drug Metabolism and Disposition November 1, 2000, 28 (11) 1267-1269;

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Rapid CommunicationShort Communication

Chronic Nifedipine Dosing Enhances Cephalexin Bioavailability and Intestinal Absorption in Conscious Rats

F. Berlioz, B. Lepére-Prevot, S. Julien, A. Tsocas, C. Carbon, C. Rozé and R. Farinotti
Drug Metabolism and Disposition November 1, 2000, 28 (11) 1267-1269;
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