Skip to content

Research at St Andrews

Genetic determinants of the pharmacokinetic variability of rifampin in Malawian adults with pulmonary tuberculosis

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Derek J. Sloan, Andrew D. McCallum, Alessandro Schipani, Deirdre Egan, Henry C. Mwandumba, Steve A. Ward, David Waterhouse, Gertrude Banda, Theresa J. Allain, Andrew Owen, Saye H. Khoo, Geraint R. Davies

School/Research organisations

Abstract

Variable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC and CES-1) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2, using a two-stage strategy to improve information during the absorption phase. In contrast to recent studies in South Africa and Uganda, SNPs in SLCO1B1 did not explain variability in AUC0-∞ of rifampin. No pharmacokinetic associations were identified with AADAC or CES-1 SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampin exposure may vary between African populations. SLCO1B1 and other novel candidate genes, as well as nongenetic sources of interindividual variability, should be further explored in geographically diverse, adequately powered cohorts.

Close

Details

Original languageEnglish
Article numbere00210-17
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017

    Research areas

  • AADAC, CES-1, Pharmacokinetics, Single nucleotide polymorphism, SLCO1B1, Tuberculosis

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. A tuberculosis molecular bacterial load assay (TB-MBLA)

    Sabiiti, W., Mtafya, B. A., Alferes De Lima, D., Dombay, E., Baron, V. O., Azam, K., Orascova, K., Sloan, D. J. & Gillespie, S. H., 6 Sep 2019, (Accepted/In press) In : Journal of Visualized Experiments.

    Research output: Contribution to journalArticle

  2. Protocol for the development of the STrengthening the Reporting of Pharmacogenetic Studies (STROPS) guideline: checklist of items for reporting pharmacogenetic studies

    Richardson, M., Kirkham, J. J., Dwan, K. M., Sloan, D. J., Davies, G. & Jorgensen, A., 11 Jul 2019, In : BMJ Open. 9, 7, 5 p., e030212.

    Research output: Contribution to journalArticle

  3. Linezolid for drug-resistant pulmonary tuberculosis

    Singh, B., Cocker, D., Ryan, H. & Sloan, D. J., 20 Mar 2019, In : Cochrane Database of Systematic Reviews. 2019, 3, CD012836.

    Research output: Contribution to journalReview article

  4. Evaluation of the efficacy of two methods for direct extraction of DNA from Mycobacterium tuberculosis sputum

    Ndhlovu, V., Mandala, W., Sloan, D., Kamdolozi, M., Caws, M. & Davies, G., 31 Dec 2018, In : Journal of Infection in Developing Countries. 12, 12, p. 1067-1072 6 p.

    Research output: Contribution to journalArticle

  5. Effect of the duration of antimicrobial exposure on the development of antimicrobial resistance (AMR) for macrolide antibiotics: protocol for a systematic review with a network meta-analysis

    Divala, T. H., Corbett, E. L., Stagg, H. R., Nliwasa, M., Sloan, D. J., French, N. & Fielding, K. L., 23 Dec 2018, In : Systematic Reviews. 7, 9 p., 246.

    Research output: Contribution to journalArticle

Related by journal

  1. Model-based relationship between the molecular bacterial load assay and time-to-positivity in liquid culture

    Svensson, R. J., Sabiiti, W., Kibiki, G. S., Ntinginya, N. E., Bhatt, N., Davies, G., Gillespie, S. H. & Simonsson, U. S. H., 29 Jul 2019, In : Antimicrobial Agents and Chemotherapy. Early

    Research output: Contribution to journalArticle

  2. Moxifloxacin replacement in contemporary tuberculosis drug regimens is ineffective against persistent Mycobacterium tuberculosis: in the Cornell mouse model

    Liu, Y., Pertinez, H., Davies, G. R., Gillespie, S. H., Coates, A. R. & Hu, Y., Jul 2018, In : Antimicrobial Agents and Chemotherapy. 62, 7, 9 p., e00190-18.

    Research output: Contribution to journalArticle

  3. TonB-dependent receptor repertoire of pseudomonas aeruginosa for uptake of siderophore-drug conjugates

    Luscher, A., Moynie, L., Auguste, P. S., Bumann, D., Mazza, L., Pletzer, D., Naismith, J. H. & Köhlera, T., Jun 2018, In : Antimicrobial Agents and Chemotherapy. 62, 6, 11 p., e00097-18.

    Research output: Contribution to journalArticle

  4. Pharmacokinetics, tolerability, and bacteriological response of rifampin administered at 600, 900, and 1,200 milligrams daily in patients with pulmonary tuberculosis

    Aarnoutse, R. E., Kibiki, G. S., Reither, K., Semvua, H. H., Haraka, F., Mtabho, C. M., Mpagama, S. G., van den Boogaard, J., Sumari-de Boer, I. M., Magis-Escurra, C., Wattenberg, M., Logger, J. G. M., te Brake, L. H. M., Hoelscher, M., Gillespie, S. H., Colbers, A., Phillips, P. P. J., Plemper van Balen, G., Boeree, M. J. & PanACEA Consortium, 1 Nov 2017, In : Antimicrobial Agents and Chemotherapy. 61, 11, e01054-17.

    Research output: Contribution to journalArticle

ID: 250563477

Top