Clinical impact of plasma concentrations of first-line antituberculosis drugs
| Autor: | R Perumal, K Naidoo, A Naidoo, N Padayatchi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | South African Medical Journal, Vol 113, Iss 3 (2023) |
| Druh dokumentu: | article |
| ISSN: | 0256-9574 2078-5135 |
| DOI: | 10.7196/SAMJ.2023.v113i3.16761 |
| Popis: | 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 TBin 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-TBdrugs (rifampicin, isoniazid, pyrazinamide and ethambutol), and had plasma drug concentrations measured at 2 and 6 hours after drugadministration during the 8th week of treatment. Intermediate (8 weeks), end-of-treatment (6 months) and follow-up TB outcomes wereassessed using World Health Organization criteria.Results. We measured plasma drug concentrations on available samples in 43 participants. Peak drug concentrations were below thetherapeutic 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%) forethambutol. At the end of the intensive phase of treatment (week 8), 20.9% (n=9/43) of participants remained culture positive. We did notfind a relationship between the concentrations of first-line drugs and treatment outcomes at week 8. All participants were cured at the endof 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. |
| Databáze: | Directory of Open Access Journals |
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