Dr. Dooley’s research focuses on clinical pharmacology of new anti-tuberculosis regimens with an emphasis on: (1) Phase I clinical trials of new or existing anti-TB drugs, including dose escalation trials and studies of drug-drug interactions between anti-TB agents and antiretrovirals to treat HIV; (2) Use of PK/PD analysis and modelling in Phase II tuberculosis clinical treatment trials to determine concentration-effect relationships that will allow for optimization of dosing; (3) Evaluation of TB and HIV drug concentrations in special populations, such as pregnant women and children; (4) Evaluation of treatment-shortening regimens for drug-sensitive TB and investigational regimens for treatment of multidrug-resistant TB; and (5) Translational work involving novel animal models of cavitary pulmonary TB disease to understand drug distribution in diseased lung.
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Svensson EM, Aweeka F, Park JG, Marzan F, Dooley KE, Karlsson MO. “Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients coinfected with HIV and tuberculosis.” Antimicrob Agents Chemother. 2013 Jun;57(6):2780-7. doi: 10.1128/AAC.00191-13. Epub 2013 Apr 9.
Svensson EM, Dooley KE, Karlsson MO. “Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection.” Antimicrob Agents Chemother. 2014 Nov;58(11):6406-12. doi: 10.1128/AAC.03246-14. Epub 2014 Aug 11.
Svensson EM, Murray S, Karlsson MO, Dooley KE. “Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.” J Antimicrob Chemother. 2015 Apr;70(4):1106-14. doi: 10.1093/jac/dku504. Epub 2014 Dec 21.
Dooley KE, Park JG, Swindells S, Allen R, Haas DW, Cramer Y, Aweeka F, Wiggins I, Gupta A, Lizak P, Qasba S, van Heeswijk R, Flexner C; ACTG 5267 Study Team. “Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267.” J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):455-62. doi: 10.1097/QAI.0b013e3182410503.
Dooley KE, Denti P, Martinson N, Cohn S, Mashabela F, Hoffmann J, Haas DW, Hull J, Msandiwa R, Castel S, Wiesner L, Chaisson RE, McIlleron H; the TSHEPISO Study Team. Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis co-infection. J Infect Dis. 2014 Jul 31. pii: jiu429. [Epub ahead of print] PMID: 25081933
Dooley KE, Luetkemeyer AF, Park JG, Allen R, Cramer Y, Murray S, Sutherland D, Aweeka F, Koletar SL, Marzan F, Bao J, Savic R, Haas DW; AIDS Clinical Trials Group (ACTG) A5306 Study Team. Phase I Safety, Pharmacokinetics, and Pharmacogenetics Study of the Anti-Tuberculosis Drug PA-824 with Concomitant Lopinavir/Ritonavir, Efavirenz, or Rifampin. Antimicrob Agents Chemother. 2014 Jun 23. pii: AAC.03332-14. [Epub ahead of print] PMID: 24957823
Savic RM, Lu Y, Bliven-Sizemore E, Weiner M, Nuermberger E, Burman W, Dorman SE, Dooley KE. Population pharmacokinetics of rifapentine and desacetyl rifapentine in healthy volunteers: nonlinearities in clearance and bioavailability. Antimicrob Agents Chemother. 2014 Jun;58(6):3035-42. doi: 10.1128/AAC.01918-13. Epub 2014 Mar 10. PMID: 24614383 [PubMed - in process]
Cherkaoui I, Sabouni R, Ghali I, Kizub D, Billioux AC, Bennani K, Bourkadi JE, Benmamoun A, Lahlou O, Aouad RE, Dooley KE. Treatment default amongst patients with tuberculosis in urban Morocco: predicting and explaining default and post-default sputum smear and drug susceptibility results. PLoS One. 2014 Apr 3;9(4):e93574. doi: 10.1371/journal.pone.0093574. eCollection 2014. PMID: 24699682 [PubMed - in process]
Williamson B, Dooley KE, Zhang Y, Back DJ, Owen A. Induction of influx and efflux transporters and cytochrome P450 3A4 in primary human hepatocytes by rifampin, rifabutin, and rifapentine. Antimicrob Agents Chemother. 2013 Dec;57(12):6366-9. doi: 10.1128/AAC.01124-13. Epub 2013 Sep 23. PMID: 24060875