[ Pharmaceutical Sciences Asia - ONLINE ]
E-ISSN 2586-8470
[ Journal Abbreviation: Pharm.Sci.Asia ]
Mahidol University Journal of Pharmaceutical Sciences
  FORMER NAME   "Mahidol University Journal of Pharmaceutical Sciences" Published Since 1974

 
Abstracts

DOI: 10.29090/psa.2021.04.20.069Pharm Sci Asia 2021; 48(4), 375-380
 

Pharmacokinetics and pharmacodynamics of low dose 300 mg once daily oral linezolid for treatment of tuberculosis

Sutep Jaruratanasirikul1*, Jetsada Piwluang2, Somchai Sriwiriyajan2,3, Monchana Nawakitrangsan1, Maseetoh Samaeng1, Nuntiya Theerapakanunt1

1 Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, Thailand
2 Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, Thailand
3 Division of Health and Applied Sciences, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, Thailand


Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis bacteria, continues to be an immense global public health problem and still remains a leading cause of death among infectious diseases, especially in developing countries. In the last few decades, the incidences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB have been increasing and have become a significant public health threat in many countries. Linezolid, an oxazolidinone antimicrobial agent, has been shown to be effective against M. tuberculosis, including MDR- and XDR-TB. However, a daily regimen of 1200 mg or even 600 mg of linezolid for treatment of MDR- and XDR-TB has potential toxicities. A daily 300 mg dose of linezolid would be an effective treatment against MDR- and XDR-TB with fewer adverse effects. The objective of this study was to determine the pharmacokinetics (PK) of a 300 mg daily dose of oral linezolid for achieving the pharmacodynamic (PD) targets. Thirty healthy subjects received 300 mg oral linezolid once daily and PK studies were carried out on day 5 after the beginning of drug administration. The mean value of AUC0-24 of this agent was calculated for the achievement of PD targets. The mean values of Vd, CL and AUC0-24 were 29.08 ± 10.75 L, 3.69 ± 1.58 L/h and 94.38 ± 35.12 mg.h/L, respectively. The AUC0-24/MIC ratio for a MIC of 0.9 and 0.75 mg/L were approximately 100 and 119, respectively. In conclusion, 300 mg of linezolid daily is an alternative antibiotic option in patients with intolerance to the side effects of the standard dosage regimens.


Keyword:

Pharmacokinetics, Pharmacodynamics, Linezolid, Tuberculosis, Multidrug- resistance




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