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September 1, 2026Frontiers in PharmacologyOpen Access

Oral SPH3127 achieves rapid absorption and extensive metabolism with ~102% excretion through feces and urine.

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Why the study?

SPH3127 is a novel direct renin inhibitor approved for hypertension in China, but its pharmacokinetics, mass balance, and biotransformation in humans required characterization.

What are the pharmacokinetics, mass balance, and metabolism of a single oral dose of [14C]SPH3127 in healthy Chinese male subjects?

Comparison

Single 100 mg oral dose of [14C]SPH3127 (100 μCi)

Design

Isotope labeling pharmacokinetic and mass balance study

Follow-up

192 h

Key result

A single 100 mg oral dose of SPH3127 was rapidly absorbed and extensively metabolized, with a mean cumulative excreted radioactivity of 101.66% primarily through feces (57.31%) and urine (44.35%).

Authors

SMSheng MaXHXintong HuangSYShu Yan

Discussion

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Member takes

Overview

Healthy volunteer PK data warrant no practice change; leaves open efficacy testing of SPH3127 in hypertension.

Structured PICO

What are the pharmacokinetics, mass balance, and metabolism of a single oral dose of [14C]SPH3127 in healthy Chinese male subjects?

P
Population
6 healthy Chinese males aged 20-30 years received a single oral dose of [14C]SPH3127 to evaluate its pharmacokinetics, mass balance, and metabolism.
I
Intervention
Single 100 mg oral dose of [14C]SPH3127 (sitokiren) (100 μCi)
O
Outcome
Pharmacokinetics, mass balance, and biotransformation of [14C]SPH3127surrogate

SPH3127 (sitokiren), a novel direct renin inhibitor, demonstrates rapid absorption and balanced elimination via urine and feces in healthy Chinese males.

Limitations

  • The structure of metabolite M524 remains unconfirmed due to the absence of a reference standard for verification.
  • Further investigation is needed to evaluate the safety of metabolites M7-4 and M8-7.
  • Hypotheses regarding gut microbiota contribution to sulfate conjugates need further exploration and validation.

Cite This Study

Ma et al. (2026) studied Healthy volunteers (n=6). [14C]SPH3127 (sitokiren) was evaluated on Mean cumulative excreted radioactivity at 192 hours. A single 100 mg oral dose of SPH3127 was rapidly absorbed and extensively metabolized, with a mean cumulative excreted radioactivity of 101.66% primarily through feces (57.31%) and urine (44.35%).

synapsesocial.com/papers/6aa60b4124014aaf7fdd5340https://doi.org/10.3389/fphar.2026.1893643
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Efficacy and Safety of SPH3127 Tablet, a Novel Direct Renin Inhibitor, in Patients with Mild-to-Moderate Essential Hypertension: A Phase III Randomised Trial2026
  2. 2A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension2024 · 4 citations
  3. 3SPH3127 (Sitokiren), a Novel Renin Inhibitor, Suppresses Colitis Development in Mouse Models of Experimental Colitis2025 · 1 citations
  4. 4The pharmacokinetics, pharmacodynamics and tolerability of SHR6508 in Chinese healthy subjects2024
  5. 5Pharmacokinetics, mass balance, and metabolism of the novel potassium-competitive acid blocker JP-1366 in healthy Chinese adults following a single oral dose of [14C]JP-13662025 · 3 citations