1. Pharmacokinetic study of two different rifabutin doses co-administered with lopinavir/ritonavir in African HIV and tuberculosis co-infected adult patients
- Author
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Tegwindé Rebeca Compaore, Paola Villani, Alberto Matteelli, Giorgia Sulis, Jacques Simpore, Serge Diagbouga, Alberto Roggi, Seni Kouanda, Mario Regazzi, Lassana Sangaré, Grissoum Tarnagda, Henri Gautier Ouedraogo, and Kadari Cisse
- Subjects
0301 basic medicine ,Male ,Rifabutin ,Lopinavir/ritonavir ,Pilot Projects ,Gastroenterology ,Lopinavir ,Random Allocation ,0302 clinical medicine ,Antibiotics ,Tandem Mass Spectrometry ,030212 general & internal medicine ,Chromatography, High Pressure Liquid ,Chromatography ,Coinfection ,Infectious Diseases ,High Pressure Liquid ,Combination ,Drug Therapy, Combination ,Female ,Burkina Faso ,HIV/tuberculosis co-infection ,Pharmacokinetic ,AIDS-Related Opportunistic Infections ,Adult ,Antibiotics, Antitubercular ,Follow-Up Studies ,HIV Protease Inhibitors ,Humans ,Microbial Sensitivity Tests ,Ritonavir ,Tuberculosis ,medicine.drug ,Research Article ,medicine.medical_specialty ,030106 microbiology ,Cmax ,Antitubercular ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Drug Therapy ,Pharmacokinetics ,Internal medicine ,medicine ,lcsh:RC109-216 ,Adult patients ,business.industry ,medicine.disease ,business - Abstract
BackgroundThis study aimed to assess the pharmacokinetic profile of 150 mg rifabutin (RBT) taken every other day (every 48 h) versus 300 mg RBT taken every other day (E.O.D), both in combination with lopinavir/ritonavir (LPV/r), in adult patients with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection.MethodsThis is a two-arm, open-label, pharmacokinetic, randomised study conducted in Burkina Faso between May 2013 and December 2015. Enrolled patients were randomised to receive either 150 mg RBT EOD (arm A, 9 subjects) or 300 mg RBT EOD (arm B, 7 subjects), both associated with LPV/r taken twice daily. RBT plasma concentrations were evaluated after 2 weeks of combined HIV and TB treatment. Samples were collected just before drug ingestion and at 1, 2, 3, 4, 6, 8, and 12 h after drug ingestion to measure plasma drug concentration using an HPLC-MS/MS assay.ResultsThe Cmax and AUC0–12hmedians in arm A (Cmax = 296 ng/mL, IQR: 205–45; AUC0–12h = 2528 ng.h/mL, IQR: 1684–2735) were lower than those in arm B (Cmax = 600 ng/mL, IQR: 403–717; AUC0–12h = 4042.5 ng.h/mL, IQR: 3469–5761), with a statistically significant difference in AUC0–12h(p = 0.044) but not in Cmax (p = 0.313). No significant differences were observed in Tmax (3 h versus 4 h). Five patients had a Cmax below the plasma therapeutic limit ( 64 ng/mL) in the 300 mg RBT arm, while 4/9 patients had such values in the 150 mg RBT arm.ConclusionThis study confirmed that the 150 mg dose of rifabutin ingested EOD in combination with LPV/r is inadequate and could lead to selection of rifamycin-resistant mycobacteria.Trial registrationPACTR201310000629390, 28th October 2013.
- Published
- 2020