RT Journal Article
SR Electronic
T1 Clarithromycin increases linezolid exposure in multidrug-resistant tuberculosis patients
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1614
OP 1621
DO 10.1183/09031936.00001913
VO 42
IS 6
A1 Mathieu S. Bolhuis
A1 Richard van Altena
A1 Dick van Soolingen
A1 Wiel C.M. de Lange
A1 Donald R.A. Uges
A1 Tjip S. van der Werf
A1 Jos G.W. Kosterink
A1 Jan-Willem C. Alffenaar
YR 2013
UL http://erj.ersjournals.com/content/42/6/1614.abstract
AB 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. Clarithromycin significantly increased linezolid serum exposure in multidrug-resistant tuberculosis patients http://ow.ly/oYGK1