title: Pharmacokinetics of rifampin in Peruvian tuberculosis patients with and without comorbid diabetes or HIV.
abstract: For drug-compliant patients, poor responses to tuberculosis (TB) treatment might be attributable to subtherapeutic drug concentrations. An impaired absorption of rifampin was previously reported for patients with diabetes mellitus (DM) or HIV. The objectives of this study were to determine whether TB drug pharmacokinetics differed in Peruvian TB patients with DM or HIV. In this cross-sectional study, TB patients, recruited from health centers in Lima, Peru, had blood samples taken at 2 and 6 h after directly observed TB drug ingestion, to determine plasma concentrations of rifampin. Of 105 patients, 50 had TB without a comorbidity, 26 had coexistent DM, and 29 had coexistent HIV. Unexpectedly, the overall median 2- and 6-h levels of rifampin were 1.6 and 3.2 mg/liter, respectively, and the time to the peak concentration was 6 h (slow absorber) instead of 2 h (fast absorber) for 61 patients (62.2%). The geometric mean peak concentration of drug in serum (C(max)) was significantly higher in fast absorbers than in slow absorbers (5.0 versus 3.8 mg/liter; P = 0.05). The rifampin C(max) was significantly lower in male patients than in female patients (3.3 versus 6.3 mg/liter; P < 0.001). Neither slow nor fast absorbers with comorbidities (DM or HIV) had significantly different C(max) results compared to those of TB patients without comorbidities. An analysis of variance regression analysis showed that female gender (P < 0.001) and the time to maximum concentration of drug in serum (T(max)) at 2 h (P = 0.012) were independently correlated with increased exposure to rifampin. Most of this Peruvian study population exhibited rifampin pharmacokinetics different from those conventionally reported, with delayed absorption and low plasma concentrations, independent of the presence of an HIV or DM comorbidity.
authors.affiliation: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru. ana.requena@cresib.cat
authors.forename: Ana
authors.initials: A
authors.lastname: Requena-Méndez
authors.forename: Geraint
authors.initials: G
authors.lastname: Davies
authors.forename: Alison
authors.initials: A
authors.lastname: Ardrey
authors.forename: Oswaldo
authors.initials: O
authors.lastname: Jave
authors.forename: Sonia L
authors.initials: SL
authors.lastname: López-Romero
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.forename: David A J
authors.initials: DA
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics*; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D012044:Regression Analysis; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics*; D012737:Sex Factors; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin