title: Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis.
abstract: Low antimycobacterial drug concentrations have been observed in tuberculosis (TB) patients under treatment. The lactulose/mannitol urinary excretion test (L/M), normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R) and isoniazid (H) were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL) or H (3-6 mcg/mL) in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.
authors.affiliation: Clinical Research Unit & Institute of Biomedicine/Center for Global Health, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Valéria G F
authors.initials: VG
authors.lastname: Pinheiro
authors.forename: Lysiane M A
authors.initials: LM
authors.lastname: Ramos
authors.forename: Helena S A
authors.initials: HS
authors.lastname: Monteiro
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Barroso
authors.forename: Oluma Y
authors.initials: OY
authors.lastname: Bushen
authors.forename: Mônica C
authors.initials: MC
authors.lastname: Façanha
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.forename: Richard L
authors.initials: RL
authors.lastname: Guerrant
authors.forename: Aldo A M
authors.initials: AA
authors.lastname: Lima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007538:Isoniazid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007792:Lactulose / Q000493:pharmacokinetics / Q000652:urine; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics / Q000652:urine; D008875:Middle Aged; D010539:Permeability; D012293:Rifampin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D008353:Mannitol; D007792:Lactulose; D007538:Isoniazid; D012293:Rifampin