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Serum Concentrations of Rifampin, Isoniazid, and Intestinal Absorption, Permeability in Patients with Multidrug Resistant Tuberculosis

This study evaluates the serum concentrations of rifampin (RMP), isoniazid (INH), and intestinal barrier function in patients with multidrug-resistant tuberculosis (MDR-TB), drug susceptible tuberculosis (DS-TB), and health volunteers (HC; controls). Peak serum concentrations of RMP were significantly lower in MDR-TB and DS-TB as compared with HC (odds ratio [OR] = 3.125, confidence interval [CI] [1.037–9.418] and OR = 4.025, CI [1.207–13.418], respectively). The INH peak serum concentration was not significantly different between MDR-TB versus DS-TB or DS-TB versus HC. The percent of mannitol excretion was significantly lower in the MDR-TB group compared with DS-TB (13.18 versus 16.03, analysis of covariance [ANCOVA], P = 0.0369) and compared with HC (13.18 versus 16.61, ANCOVA, P = 0.0291) the other study groups. These data suggested a lower peak serum concentration of RMP for both MDR-TB and DS-TB as compared with the HC group. The data also showed a lower intestinal area of absorption in patients with tuberculosis and even worse in MDR-TB.

Received January 24, 2009. Accepted for publication April 22, 2009.

Acknowledgments: We are grateful to the patients, healthy volunteers, staff of the Messejana’s Hospital tuberculosis outpatient service and Clinical Research Unit & Institute of Biomedicine, School of Medicine, Federal University of Ceará, Fortaleza, Ce, Brazil for their assistance in the completion of the research protocol.

Financial support: This work was supported by grant numbers 233/06 and 473997/2006-1 from Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico (FUNCAP, CE, Brasil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Ministério da Ciência e Tecnologia, MCT–CNPq, Brasília, DF, Brazil.

^* Address correspondence to Aldo A. M. Lima, INCT—Institute of Biomedicine/Center for Global Health, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. R. Cel. Nunes de Melo, No. 1315, Rodolfo Teófilo, CEP 60.430-270, Fortaleza, Ceará, Brazil. E-mail: alima{at}ufc.br

Authors’ addresses: Elizabeth C. Barroso, Valéria G. F. Pinheiro, Mônica C. Façanha, Maria R. D. Carvalho, Maria E. Moura, Creusa L. Campelo, and Aldo A. M. Lima, INCT—Institute of Biomedicine/Center for Global Health, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil, R. Cel. Nunes de Melo, No. 1315, Rodolfo Teófilo, CEP 60.430-270, Fortaleza, Ceará, Brazil, Tel/Fax: 55(85)3366 8445, E-mails: ybarroso{at}fortalnet.com.br , valeria.goes{at}terra.com.biz , mfacanha{at}ufc.br , romidantas{at}hotmail.com , tisiologia{at}hm.ce.gov.br , creusalima{at}hotmail.com , and alima{at}ufc.br . Charles A. Peloquin, College of Pharmacy and Emerging Pathogens Institute, University of Florida, 1600 SW Archer Rd., Rm P4-33, Gainesville, FL 32610-0486, Tel: 353-272-6266, E-mail: peloquin{at}cop.ufl.edu . Richard L. Guerrant, Center for Global Health, University of Virginia, MR6, Carter Harrison Building, 345 Crispell Drive, Room 2520, Charlottesville, VA 22908-1379, Tel: 434-924-4672, E-mail: rlg9a{at}virginia.edu .