MDR & XDR TB

Dosage Regimens & Effectiveness

A comparison of the pharmacokinetics was done for two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients.  Linezolid is a promising drug, but its use is limited by adverse effects with prolonged administration of 600 mg twice daily.  In order to reduce its adverse effects and maintain efficacy, the researchers[1] investigated whether linezolid in a reduced dosage resulted in drug serum concns. exceeding a ratio of the in vitro min. inhibitory concn. (MIC) to the area under the serum concn.-time curve (AUC) over 24 h (AUC24) [AUC24/MIC] of >100.  This open-label, prospective pharmacokinetic study evaluated two doses (300 and 600 mg) of linezolid in MDR-TB patients, who received linezolid as part of their treatment.  They received linezolid 300 mg twice daily for 3 days, followed by 600 mg twice daily.  Blood samples taken at predefined intervals for measuring serum linezolid concns. were processed by a validated liq. chromatog.-tandem mass spectrometry procedure.  The AUC24/MIC ratio was used as a predictive model of efficacy.  Adverse effects of linezolid, including peripheral neuropathy, were evaluated by clin. and lab. assessments.  Eight patients were included in this study.  The median duration of linezolid treatment was 56 days (interquartile range [IQR 44-82] days), with a median cumulative dose of 51,000 mg (IQR 33 850-60 450 mg).  The median linezolid AUC over 12 h (AUC12) values were 57.6 mg/h/L (IQR 38.5-64.2 mg/h/L) with the 300 mg dose and 145.8 mg/h/L (IQR 101.2-160.9 mg/h/L) with the 600 mg dose.  The AUC24/MIC ratios were 452 (IQR 343-513) with the 300 mg dose and 1151 (IQR 656-1500) with the 600 mg dose.  Linezolid was well tolerated.  Seemingly effective serum concns. were reached after 3 days of administration of linezolid 300 mg twice daily, i.e. the AUC24/MIC ratio was at least 100 in 7 of 8 patients.  According to the authors, larger nos. of patients should be studied to confirm the efficacy of the linezolid 300 mg twice-daily dosage in MDR-TB or XDR-TB treatment. 


Key Words:  multidrug resistant tuberculosis, extensively drug resistant tuberculosis, multidrug resistant TB,  extensively drug resistant TB, MDR TB, XDR TB, mycobacterium tuberculosis, mycobacterial infection, literature, research, publications, patents.

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[1] Alffenaar, Jan-Willem C et al., (Department of Hospital and Clinical Pharmacy and Toxicology, University Medical Center Groningen, University of Groningen, Groningen, Neth.), Clinical Pharmacokinetics, 49(8), 559-565 (English) 2010.