n South African Medical Journal - The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care : research

Volume 103, Issue 6
  • ISSN : 0256-9574
  • E-ISSN: 2078-5135



There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically ill patients.

To establish the pharmacokinetic profile of a fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol given according to weight via a nasogastric tube to patients admitted to an intensive care unit (ICU).
We conducted a prospective, observational study on 10 patients (mean age 32 years, 6 male) admitted to an ICU and treated for tuberculosis (TB). Serum concentrations of the drugs were determined at eight predetermined intervals over 24 hours by means of high-performance liquid chromatography.
The therapeutic maximum plasma concentration (C) for rifampicin at time to peak concentration was achieved in only 4 patients, whereas 2 did not achieve therapeutic C for isoniazid. No patient reached sub-therapeutic C for pyrazinamide (6 were within and 4 above therapeutic range). Three patients reached sub-therapeutic C for ethambutol, and 6 patients were within and 1 above the therapeutic range. Patients with a sub-therapeutic rifampicin level had a higher mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score (=0.03) and a lower estimated glomerular filtration rate (GFR) (=0.03).
A fixed-dose combination tablet, crushed and mixed with water, given according to weight via a nasogastric tube to patients with TB admitted to an ICU resulted in sub-therapeutic rifampicin plasma concentrations in the majority of patients, whereas the other drugs had a more favourable pharmacokinetic profile. Patients with a sub-therapeutic rifampicin concentration had a higher APACHE II score and a lower estimated GFR, which may contribute to suboptimal outcomes in critically ill patients. Studies in other settings have reported similar proportions of patients with 'sub-therapeutic' rifampicin concentrations.

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