Mycophenolate mofetil for systemic sclerosis: drug exposure exhibits considerable inter-individual variation-a prospective, observational study.

ABSTRACT: OBJECTIVE:Mycophenolate mofetil (MMF) is an established therapy for systemic sclerosis (SSc), but its pharmacokinetics in this disease remains unexplored. We have investigated drug exposure in MMF-treated patients with SSc in relation to clinical features of the disease and common concomitant drugs. METHODS:This study was predefined to include 35 MMF-treated SSc patients who were using MMF at a fixed dose of 0.5, 1.0 or 1.5?g twice daily since at least 3?months. The 12-h drug exposure of the active MMF metabolite mycophenolic acid (MPA) was estimated by repeated analysis of plasma MPA over a 6-h period. This 12-h drug exposure was dose normalised to a daily intake of 3?g MMF (MPA_AUC3g) in order to compare subjects using MMF at different doses. Drug exposure was analysed in reference to the clinical characteristics including body weight, renal function, autoantibodies, intestinal dysbiosis, intestinal inflammation assessed by faecal (F)-calprotectin, intestinal symptoms assessed by the University of California Los Angeles Scleroderma Trial Consortium Gastrointestinal Tract Instrument 2.0 and concomitant drug usage including proton-pump inhibitors (PPI). RESULTS:Thirty-four out of 35 study participants completed the study. The mean daily MMF dose was 2.1?g. Drug exposure expressed as MPA_AUC3g varied up to 8-fold between patients (median 115, range 27-226?mg h/L). MPA_AUC3g was inversely related to body weight (rs?=?-?0.58, p?

SUBMITTER: Andreasson K 

PROVIDER: S-EPMC7539387 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature