title: Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana.
abstract: BACKGROUND
  We conducted a pharmacokinetic study of antimycobacterial drugs involving a cohort of patients with pulmonary tuberculosis (TB) in Gaborone, Botswana, to assess the prevalence of and risk factors for low drug concentrations in serum.
  
  
  METHODS
  Adults participated if they had a history of cough > or =2 weeks, had abnormal chest radiograph findings, consented to testing for human immunodeficiency virus (HIV), had sputum cultures positive for Mycobacterium tuberculosis, and were receiving antituberculous therapy for >7 days. Observed maximum serum concentrations were compared with published normal ranges. RESULTS. Of 91 patients enrolled, 89 (98%) were outpatients, and 59 (68%) of 87 patients tested had HIV infection. The following numbers of patients had low serum concentrations of the following drugs: isoniazid, 27 (30%) of 90; rifampin, 71 (78%) of 91; ethambutol, 37 (41%) of 91; and pyrazinamide, 1 (1%) of 91. Low serum concentrations of both isoniazid and rifampin occurred in 23 (26%) of 90 patients. Low serum concentrations of rifampin were found in both HIV-infected and non-HIV-infected patients, and such patients were less likely to have >4 weeks of symptoms, more likely to have lymphadenopathy, and more likely to have low serum albumin levels (P<.05 for all). The associations with noncavitary pulmonary disease (P=.12) and HIV infection (P=.07) did not reach statistical significance. Delayed absorption was most common with ethambutol, followed by rifampin.
  
  
  CONCLUSIONS
  These data, predominantly from HIV-infected patients with TB, suggest that low isoniazid, rifampin, and ethambutol concentrations are common in Botswana. In contrast, pyrazinamide usually is well absorbed.
authors: Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors: Jordan W
authors: JW
authors: Tappero
authors: Williamson Z
authors: WZ
authors: Bradford
authors: Tracy B
authors: TB
authors: Agerton
authors: Philip
authors: P
authors: Hopewell
authors: Arthur L
authors: AL
authors: Reingold
authors: Shahin
authors: S
authors: Lockman
authors: Aderonke
authors: A
authors: Oyewo
authors: Elizabeth A
authors: EA
authors: Talbot
authors: Thomas A
authors: TA
authors: Kenyon
authors: Themba L
authors: TL
authors: Moeti
authors: Howard J
authors: HJ
authors: Moffat
authors: Charles A
authors: CA
authors: Peloquin
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001902:Botswana; D015897:Comorbidity; D004977:Ethambutol / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics; D008297:Male; D011718:Pyrazinamide / Q000493:pharmacokinetics; D012293:Rifampin / Q000493:pharmacokinetics; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000150:complications / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin