Pharmacokinetics, safety, and dose optimization of GST-HG171 in renal impairment: insights from physiologically based pharmacokinetic modeling.

Publication date: Jul 15, 2026

GST-HG171 is an orally administered inhibitor of the 3C-like protease that has been approved in China for the treatment of mild to moderate COVID-19. When co-administered with ritonavir, GST-HG171 is eliminated by the kidney. Therefore, this study evaluated the impact of renal impairment on its pharmacokinetics (PK), safety, and tolerability. A total of 24 participants were enrolled: 8 with normal renal function, 8 with mild renal impairment, and 8 with moderate renal impairment. Participants received 100 mg ritonavir at -12, 0, 12, and 24 h, with a single 150 mg dose of GST-HG171 co-administered at 0 h to maintain CYP3A inhibition. Compared with healthy subjects, mild renal impairment increased GST-HG171 exposure; the geometric least-squares mean ratios (90% confidence intervals) for C, AUC, and AUC were 118. 15 (99. 38-140. 46), 139. 48 (111. 21-174. 95), and 138. 46 (111. 19-172. 42), respectively. Moderate impairment further increased exposure, with ratios of 131. 81 (108. 34-160. 36), 186. 18 (150. 47-230. 36), and 182. 64 (148. 03-225. 33), respectively. Renal clearance was reduced by 22. 7% and 52% in the mild and moderate impairment groups, respectively. GST-HG171 was generally tolerated across all groups, but adverse reactions related to hypertriglyceridemia should be monitored. Physiologically based PK modeling supported dose reductions for patients with renal impairment, recommending GST-HG171/ritonavir 100/100 mg twice daily for mild impairment and 50/100 mg twice daily for moderate impairment, administered for 5 days. CLINICAL TRIALSThis study is registered with ClinicalTrials. gov as NCT06106126.

Concepts Keywords
clinical trial
COVID-19
GST-HG171
PBPK
pharmacokinetics
renal impairment
safety

Semantics

Type Source Name
disease MESH COVID-19
drug DRUGBANK Ritonavir
disease MESH hypertriglyceridemia

Original Article

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Pharmacokinetics, safety, and dose optimization of GST-HG171 in renal impairment: insights from physiologically based pharmacokinetic modeling.

Publication date: Jul 15, 2026

GST-HG171 is an orally administered inhibitor of the 3C-like protease that has been approved in China for the treatment of mild to moderate COVID-19. When co-administered with ritonavir, GST-HG171 is eliminated by the kidney. Therefore, this study evaluated the impact of renal impairment on its pharmacokinetics (PK), safety, and tolerability. A total of 24 participants were enrolled: 8 with normal renal function, 8 with mild renal impairment, and 8 with moderate renal impairment. Participants received 100 mg ritonavir at -12, 0, 12, and 24 h, with a single 150 mg dose of GST-HG171 co-administered at 0 h to maintain CYP3A inhibition. Compared with healthy subjects, mild renal impairment increased GST-HG171 exposure; the geometric least-squares mean ratios (90% confidence intervals) for C, AUC, and AUC were 118. 15 (99. 38-140. 46), 139. 48 (111. 21-174. 95), and 138. 46 (111. 19-172. 42), respectively. Moderate impairment further increased exposure, with ratios of 131. 81 (108. 34-160. 36), 186. 18 (150. 47-230. 36), and 182. 64 (148. 03-225. 33), respectively. Renal clearance was reduced by 22. 7% and 52% in the mild and moderate impairment groups, respectively. GST-HG171 was generally tolerated across all groups, but adverse reactions related to hypertriglyceridemia should be monitored. Physiologically based PK modeling supported dose reductions for patients with renal impairment, recommending GST-HG171/ritonavir 100/100 mg twice daily for mild impairment and 50/100 mg twice daily for moderate impairment, administered for 5 days. CLINICAL TRIALSThis study is registered with ClinicalTrials. gov as NCT06106126.

Concepts Keywords
clinical trial
COVID-19
GST-HG171
PBPK
pharmacokinetics
renal impairment
safety

Semantics

Type Source Name
disease MESH COVID-19
drug DRUGBANK Ritonavir
disease MESH hypertriglyceridemia

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *

Pharmacokinetics, safety, and dose optimization of GST-HG171 in renal impairment: insights from physiologically based pharmacokinetic modeling.

Publication date: Jul 15, 2026

GST-HG171 is an orally administered inhibitor of the 3C-like protease that has been approved in China for the treatment of mild to moderate COVID-19. When co-administered with ritonavir, GST-HG171 is eliminated by the kidney. Therefore, this study evaluated the impact of renal impairment on its pharmacokinetics (PK), safety, and tolerability. A total of 24 participants were enrolled: 8 with normal renal function, 8 with mild renal impairment, and 8 with moderate renal impairment. Participants received 100 mg ritonavir at -12, 0, 12, and 24 h, with a single 150 mg dose of GST-HG171 co-administered at 0 h to maintain CYP3A inhibition. Compared with healthy subjects, mild renal impairment increased GST-HG171 exposure; the geometric least-squares mean ratios (90% confidence intervals) for C, AUC, and AUC were 118. 15 (99. 38-140. 46), 139. 48 (111. 21-174. 95), and 138. 46 (111. 19-172. 42), respectively. Moderate impairment further increased exposure, with ratios of 131. 81 (108. 34-160. 36), 186. 18 (150. 47-230. 36), and 182. 64 (148. 03-225. 33), respectively. Renal clearance was reduced by 22. 7% and 52% in the mild and moderate impairment groups, respectively. GST-HG171 was generally tolerated across all groups, but adverse reactions related to hypertriglyceridemia should be monitored. Physiologically based PK modeling supported dose reductions for patients with renal impairment, recommending GST-HG171/ritonavir 100/100 mg twice daily for mild impairment and 50/100 mg twice daily for moderate impairment, administered for 5 days. CLINICAL TRIALSThis study is registered with ClinicalTrials. gov as NCT06106126.

Concepts Keywords
clinical trial
COVID-19
GST-HG171
PBPK
pharmacokinetics
renal impairment
safety

Semantics

Type Source Name
disease MESH COVID-19
drug DRUGBANK Ritonavir
disease MESH hypertriglyceridemia

Original Article

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