title: Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB.
abstract: OBJECTIVE
  Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion.
  
  
  METHODS
  The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (μg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001).
  
  
  CONCLUSIONS
  The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.
authors.affiliation: Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Seung Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Seo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Je Hyeong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Pulmonary, Sleep, and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
authors.forename: Chol
authors.initials: C
authors.lastname: Shin
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Jong-Ryul
authors.initials: JR
authors.lastname: Ghim
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea. dhkim@inje.ac.kr.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003523:Cycloserine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D055118:Medication Adherence; D008875:Middle Aged; D000077266:Moxifloxacin; D011515:Prothionamide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012189:Retrospective Studies; D013183:Sputum / Q000382:microbiology*; D053719:Tandem Mass Spectrometry; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D011515:Prothionamide; D003523:Cycloserine; D000077266:Moxifloxacin
keywords: Tuberculosis; cycloserine; drug monitoring; moxifloxacin; multidrug resistance; prothionamide