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Purpose <p>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.</p> Materials and methods <p>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&#xa0;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.</p> Results <p>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&#xa0;μg/mL.h) and was comparable between the three dose groups when normalized to dose (AUC/dose: 182–189&#xa0;μg/mL/g.h) and to non-Japanese (168–183&#xa0;μg/mL.h). The mean terminal half-life (1.43–1.86&#xa0;h), and the distribution volume (11.3–15.2&#xa0;L) were also similar to those of non-Japanese healthy volunteers (1.50–1.73&#xa0;h and 13.0–15.5&#xa0;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&#xa0;h after administration. The mean total clearance was comparable between the different administered doses (5.3–5.6&#xa0;L/h) and similar to the mean renal clearance. No gadopiclenol-related AEs were reported.</p> Conclusions <p>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.</p>

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Pharmacokinetics and safety of gadopiclenol in Japanese healthy volunteers

  • 期刊论文

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  • 发表日期：

    2025年7月29日

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  • Takashi Eto,
  • Toshiaki Taoka,
  • Mathieu Felices,
  • Camille Pitrou

摘要

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.