The original publication is available at http://www.samj.org.zaBackground. There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically
ill patients.
Objectives. 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).
Methods. 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 highperformance
liquid chromatography.
Results. The therapeutic maximum plasma concentration (Cmax) for rifampicin at time to peak concentration was achieved in only 4
patients, whereas 2 did not achieve therapeutic Cmax for isoniazid. No patient reached sub-therapeutic Cmax for pyrazinamide (6 were within
and 4 above therapeutic range). Three patients reached sub-therapeutic Cmax 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 (p=0.03) and a lower estimated glomerular filtration rate (GFR) (p=0.03).
Conclusions. 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.Publishers' Versio
