Trial reportAntimicrobial agents and chemotherapy2014
Pharmacokinetics of para-aminosalicylic acid in HIV-uninfected and HIV-coinfected tuberculosis patients receiving antiretroviral therapy, managed for multidrug-resistant and extensively drug-resistant tuberculosis.
Trial report in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Mutations inJAC-antimicrobial resistance · 2026Article
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- The microevolutionary trajectory of endemic multidrug-resistant tuberculosis strains in Portugal toward increased drug resistance levels and its clinical significance.Frontiers in microbiology · 2025Article
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Pharmacokinetics and Dose Optimization Strategies of Para-Aminosalicylic Acid in Children with Rifampicin-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Clinical standards for the dosing and management of TB drugs.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2022Article
- Synthesis and biological evaluation of orally active prodrugs and analogs of para-aminosalicylic acid (PAS).European journal of medicinal chemistry · 2022Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- The pharmacokinetics of para-aminosalicylic acid and its relationship to efficacy and intolerance.British journal of clinical pharmacology · 2020Review
- Probability of mycobactericidal activity of para-aminosalicylic acid with novel dosing regimens.European journal of clinical pharmacology · 2020Article
- Integrated population pharmacokinetics of etirinotecan pegol and its four metabolites in cancer patients with solid tumors.Cancer chemotherapy and pharmacology · 2018Article
- Current therapies for the treatment of multidrug-resistant tuberculosis in children in India.Expert opinion on pharmacotherapy · 2017Review
- Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities.Antimicrobial agents and chemotherapy · 2017Article
- Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae.Antimicrobial agents and chemotherapy · 2016Article
- Characterization of 22 Antituberculosis Drugs for Inhibitory Interaction Potential on Organic Anionic Transporter Polypeptide (OATP)-Mediated Uptake.Antimicrobial agents and chemotherapy · 2016Article
- N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis prompted the reintroduction of para-aminosalicylic acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is required. Out of necessity, patients receive multiple drugs, and PAS therapy is frequent; however, neither potential drug interactions nor the effects of HIV infection are known. Potential drug-drug interaction with PAS and the effect of HIV infection was examined in 73 pulmonary tuberculosis patients; 22 (30.1%) were HIV coinfected. Forty-one pulmonary MDR or XDR tuberculosis patients received 4 g PAS twice daily, and in a second crossover study, another 32 patients were randomized, receiving 4 g PAS twice daily or 8 g PAS once daily. A PAS population pharmacokinetic model in two dosing regimens was developed; potential covariates affecting its pharmacokinetics were examined, and Monte Carlo simulations were conducted evaluating the pharmacokinetic-pharmacodynamic index. The probability of target attainment (PTA) to maintain PAS levels above MIC during the dosing interval was estimated by simulation of once-, twice-, and thrice-daily dosing regimens not exceeding 12 g daily. Concurrent efavirenz (EFV) medication resulted in a 52% increase in PAS clearance and a corresponding >30% reduction in mean PAS area under the concentration curve in 19 of 22 HIV-M. tuberculosis-coinfected patients. Current practice recommends maintenance of PAS concentrations at ≥1 μg/ml (the MIC of M. tuberculosis), but the model predicts that at only a minimum dose of 4 g twice daily can this PTA be achieved in at least 90% of the population, whether or not EFV is concomitantly administered. Once-daily dosing of 12 g PAS will not provide PAS concentrations exceeding the MIC over the entire dosing interval if coadministered with EFV, while 4 g twice daily ensures concentrations exceeding MIC over the entire dosing interval, even in HIV-infected patients who received EFV.
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