Pharmacokinetics and tolerability of one-month daily rifapentine for latent tuberculosis treatment in haemodialysis patients

Abstract Background A one-month regimen of daily isoniazid plus rifapentine (1HP) is endorsed by WHO for latent tuberculosis infection (LTBI), showing efficacy and safety in people with human immunodeficiency virus (HIV). However, the pharmacokinetics (PK) of rifapentine in end-stage renal disease (ESRD) patients on dialysis remain unknown. Methods We conducted a 24-hour multiple-dose PK study of daily rifapentine in 11 dialysis-dependent patients with LTBI. Participants received rifapentine 450–600 mg plus isoniazid 300 mg daily for 4 weeks. Plasma samples were collected on day 14 at eight time points: pre-dose and 1, 2, 4, 6, 8, 12 and 24 hours post-dose. Rifapentine concentrations were measured using validated HPLC. PK parameters were compared with historical cohort from non-dialysed populations. Results Participants (63% male, mean age 49) received a mean rifapentine dose of 9.9 ± 1.6 mg/kg. Eleven (69%) completed treatment; five discontinued due to adverse events or transplantation. Median maximum concentration (Cmax) was 11.4 µg/mL (IQR, 8.7–13.7); median AUC0–24 was 177 µg·h/mL (IQR, 134–206). Conclusions Rifapentine exposure in dialysis patients was lower than in non-dialysed historical cohorts, highlighting the need for larger studies to refine dosing in this population.