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Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients.
Bolhuis, Mathieu S; van Altena, Richard; van Soolingen, Dick; de Lange, Wiel C M; Uges, Donald R A; van der Werf, Tjip S; Kosterink, Jos G W; Alffenaar, Jan-Willem C.
Afiliação
  • Bolhuis MS; University of Groningen, University Medical Centre Groningen, Groningen.
Eur Respir J ; 42(6): 1614-21, 2013 Dec.
Article em En | MEDLINE | ID: mdl-23520311
ABSTRACT
The use of linezolid for the treatment of multidrug-resistant tuberculosis is limited by dose- and time-dependent toxicity. Recently, we reported a case of pharmacokinetic drug-drug interaction between linezolid and clarithromycin that resulted in increased linezolid exposure. The aim of this prospective pharmacokinetic study is to quantify the effect of clarithromycin on the exposure of linezolid. Subjects were included in an open-label, single-centre, single-arm, fixed-order pharmacokinetic interaction study. All subjects received 300 mg linezolid twice daily during the entire study, consecutively co-administered with 250 mg and 500 mg clarithromycin once daily. Steady-state serum curves of linezolid and clarithromycin were analysed using validated methods, and differences between pharmacokinetic parameters were calculated. Linezolid exposure increased by a median (interquartile range) of 44% (23-102%, p=0.043) after co-administration of 500 mg clarithromycin (n=5) compared to baseline, whereas 250 mg clarithromycin had no statistically significant effect. Co-administration was well tolerated by most patients; none experienced severe adverse effects. One patient reported common toxicity criteria grade 2 gastrointestinal adverse events. In this study, we showed that clarithromycin significantly increased linezolid serum exposure after combining clarithromycin with linezolid in multidrug-resistant tuberculosis patients. The drug-drug interaction is possibly P-glycoprotein-mediated. Due to large interpatient variability, therapeutic drug monitoring is advisable to determine individual effect size.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Claritromicina / Tuberculose Resistente a Múltiplos Medicamentos / Oxazolidinonas / Acetamidas / Antituberculosos Tipo de estudo: Observational_studies / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur Respir J Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Claritromicina / Tuberculose Resistente a Múltiplos Medicamentos / Oxazolidinonas / Acetamidas / Antituberculosos Tipo de estudo: Observational_studies / Prognostic_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur Respir J Ano de publicação: 2013 Tipo de documento: Article