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PA-067
PHARMACOKINETICS OF RIFABUTIN IN COMBINATION WITH LOPINAVIR-RITONAVIR IN ADULT PATIENTS WITH HIV AND TUBERCULOSIS CO-INFECTION IN BURKINA FASO
  1. Henri Gautier Ouedraogo1,
  2. Alberto Matteelli2,
  3. Mario Regazzi3,
  4. Grissoum Tarnagda1,
  5. Paola Villani3,
  6. Giorgia Sulis2,
  7. Serge Diagbouga1,
  8. Alberto Roggi2,
  9. Francesco Giorgetti4,
  10. Seni Kouanda1
  1. 1IRSS, Burkina Faso
  2. 2Institute of Infectious and Tropical Diseases, Spedali Civili, Brescia, Italy
  3. 3Fondazione IRCCS Policlinico San Matteo, Italy
  4. 4National TB Program, Burkina Faso

Abstract

Background This study aimed to assess the pharmacokinetic profile of rifabutin (RBT) given at 150 mg or 300 mg every other day (EOD) in tuberculosis (TB)-HIV co-infected adult patients.

Methods This is a pharmacokinetic prospective, pilot, open, randomised study of two doses of RBT in combination with lopinavir/ritonavir among HIV−TB patients in Burkina. Sixteen patients were randomised in two arms: TB treatment consisting HZE standard doses in association with RBT150 mg EOD (arm A, 8 patients) or RBT300 mg EOD (arm B, 8 patients) in combination with lopinavir/ritonavir. RBT plasma concentrations were evaluated after two weeks of combined HIV and TB treatment. Samples were collected at pre-dosing and at 1, 2, 3, 4, 6, 8 and12 hours after drug ingestion to measure plasma drug concentration using HPLC–MS/MS assay.

Results The mean Cmax and AUC in the RBT 150 mg arm (Cmax=0.35±0,18 µg/mL, AUC(0–24)=3.94±2,1 µg.h/mL) were significantly lower (p=0.01) than those of the RBT 300 mg arm (Cmax=0.75±0.54 µg/mL AUC(0–24)=7.1±2.7 µg.h/mL). There was no significant difference in Tmax (Tmax=3.44±2.01 hours vs Tmax=3.86±2.04 hours) p=0.687. RBT follows linear kinetics and no significant differences were apparent in the mean oral clearance (CL/F) estimates (p=0.683), which were dose independent and similar for the 2 assessment doses. Five of 8 patients in RBT150 mg arm had a Cmax below plasma therapeutic limit (<0.3 µg/ml). All patients in RBT 300 mg arm had a higher Cmax than this limit. Also, at 48 hours of drug ingestion, all patients in the RBT 300 mg arm (8/8) had a mycobacterial minimum inhibitory concentration (MIC) above the limit (>0.06 µg/mL) compared with 4 of 8 patients in the RBT150 mg arm. The means Cmax, AUC (0–24) and Tmax of 25-O-desacetyl rifabutin of the RBT 300 mg arm were increased by 100% and 50% respectively compared to the RBT150 mg arm.

Conclusions This study confirmed that the dose of rifabutin 150 mg three times a week in combination with lopinavir/ ritonavir is inadequate and could lead to the selection of rifamycin-resistant mycobacteria.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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