Clinical impact of plasma concentrations of first-line antituberculosis drugs
DOI:
https://doi.org/10.7196/SAMJ.2023.v113i3.16761Keywords:
HIV, TB, TherapeuticAbstract
Background. The clinical significance of low antituberculosis (anti-TB) drug concentrations has not been fully elucidated.
Objectives. To investigate the clinical consequences of first-line drug concentrations in adult patients with drug-susceptible pulmonary TB
in South Africa (SA).
Method. We conducted a pharmacokinetic study nested within the control arm of the Improving Treatment Success (IMPRESS) trial
(NCT 02114684) in Durban, SA. During the first 2 months of treatment, participants received weight-based dosing of first-line anti-TB
drugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drug
administration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes were
assessed using World Health Organization criteria.
Results. We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below the
therapeutic range in 39/43 (90.7%) for rifampicin, 32/43 (74.4%) for isoniazid, 27/42 (64.3%) for pyrazinamide and 5/41 (12.2%) for
ethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did not
find a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the end
of treatment, and there were no relapses during the 12-month follow-up period.
Conclusion. Treatment outcomes were favourable despite low drug concentrations as defined by current reference thresholds.
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