Pharmacokinetics and safety of gadopiclenol in Japanese healthy volunteers

Abstract Purpose The aim of this study was to evaluate the pharmacokinetics and safety of gadopiclenol in Japanese healthy volunteers. A population-based pharmacokinetic approach was used to compare pharmacokinetic parameters with a non-Japanese adult population. Materials and methods In this double-blind, placebo-controlled phase I study, Japanese healthy volunteers were randomized to receive gadopiclenol (at 0.025, 0.05, or 0.1 mmol/kg) or a placebo. Blood and urine samples were collected up to 24- and 48-h post-administration, respectively. The pharmacokinetic profile of gadopiclenol was evaluated using standard non-compartmental analysis. Adverse events (AEs) were collected during the whole study period. Results Overall, 27 participants were randomized (median [range] age: 22 [20–43] years; 52% male): 18 received gadopiclenol (6 in each dose group), and 9 received the placebo. The mean systemic exposure of gadopiclenol increased proportionally with the injected dose (area under the curve [AUC]: 215–1034 μg/mL.h) and was comparable between the three dose groups when normalized to dose (AUC/dose: 182–189 μg/mL/g.h) and to non-Japanese (168–183 μg/mL.h). The mean terminal half-life (1.43–1.86 h), and the distribution volume (11.3–15.2 L) were also similar to those of non-Japanese healthy volunteers (1.50–1.73 h and 13.0–15.5 L, respectively). The mean fraction of gadopiclenol excreted in urine was between 87 and 95%, depending on the administered dose. Most of gadopiclenol (median of 95.7%) was excreted within 24 h after administration. The mean total clearance was comparable between the different administered doses (5.3–5.6 L/h) and similar to the mean renal clearance. No gadopiclenol-related AEs were reported. Conclusions The pharmacokinetic profile of gadopiclenol is similar in Japanese and non-Japanese healthy volunteers. The population pharmacokinetic analysis showed no significant ethnic disparities between these two populations and suggested that no dose adjustment was required for Japanese patients. Gadopiclenol had a very good tolerability in Japanese healthy volunteers with no adverse reactions reported.