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Pharmacokinetic interaction between levofloxacin and ciclosporin or tacrolimus in kidney transplant recipients: ciclosporin, tacrolimus and levofloxacin in renal transplantation.
Federico, Stefano; Carrano, Rosa; Capone, Domenico; Gentile, Antonio; Palmiero, Giuseppe; Basile, Vincenzo.
Afiliación
  • Federico S; Department of Systematic Pathology, Section of Renal Transplantation, Faculty of Medicine and Surgery, 'Federico II' University of Naples, Naples, Italy. federico@unina.it
Clin Pharmacokinet ; 45(2): 169-75, 2006.
Article en En | MEDLINE | ID: mdl-16485913
ABSTRACT
BACKGROUND AND

OBJECTIVE:

Bacterial infections are common complications after organ transplantation. Fluoroquinolones are frequently used for treatment because of their broad spectrum of activity; but some of them, such as ciprofloxacin and norfloxacin, are reported to increase blood concentration of ciclosporin because they are metabolised by the liver through the same enzymatic pathway, the cytochrome P450 system. This study was performed to establish whether levofloxacin, a more recent fluoroquinolone that undergoes limited hepatic metabolism, interferes with metabolism and excretion of either ciclosporin microemulsion or tacrolimus.

METHODS:

Pharmacokinetic studies were carried out in two groups of renal transplant patients, on either ciclosporin or tacrolimus treatment, before and at the sixth day of treatment with levofloxacin.

RESULTS:

Levofloxacin significantly increased the mean area under the blood concentration-time curve (AUC) and the other pharmacokinetic parameters of ciclosporin and tacrolimus by about 25%. The interference of levofloxacin on the hepatic metabolism of these drugs was demonstrated by the concomitant decrease by 5% of polyclonal ciclosporin concentration, which is the expression of parent drug and its metabolites. Both before and during levofloxacin treatment we observed trough concentrations of monoclonal and polyclonal ciclosporin significantly lower in the evening (C(12)) than in the morning (C(0)); this observation suggests a circadian variation in the metabolism of this drug. However, no difference between C(0) and C(12) was observed with tacrolimus, confirming its more predictable bioavailability.

CONCLUSION:

Our data demonstrate that levofloxacin partially inhibits the metabolism of both ciclosporin microemulsion and tacrolimus, and therefore close therapeutic monitoring of these two drugs should be recommended during levofloxacin therapy.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ofloxacino / Trasplante de Riñón / Tacrolimus / Ciclosporina / Levofloxacino / Inmunosupresores / Antibacterianos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Clin Pharmacokinet Año: 2006 Tipo del documento: Article País de afiliación: Italia
Buscar en Google
Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ofloxacino / Trasplante de Riñón / Tacrolimus / Ciclosporina / Levofloxacino / Inmunosupresores / Antibacterianos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Clin Pharmacokinet Año: 2006 Tipo del documento: Article País de afiliación: Italia