Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment
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2025
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| _version_ | 1867016208442720256 |
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| author | Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao |
| author_facet | Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao |
| collection | Wiley Open Access |
| contents | Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao British Journal of Clinical Pharmacology Aims Crisugabalin is a novel calcium channel α2δ subunit ligand and a highly selective oral gamma‐aminobutyric acid (GABA) analogue developed for the treatment of diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). This study investigated pharmacokinetic properties and safety of crisugabalin in subjects with renal impairment. Methods This multicenter, nonrandomized, open‐label Phase I study investigated the pharmacokinetics and safety of a single oral 20‐mg dose of crisugabalin capsule in Chinese subjects with various degrees of renal function, categorized according to the absolute glomerular filtration rate (GFR). A total of 32 subjects (eight subjects per renal function category [normal, mild, moderate, or severe impairment]) were enrolled and completed the study. Blood samples were collected up to 72 h post‐dose, along with fractionated urine samples. Active moiety exposures were calculated as the sum of unbound exposures for crisugabalin and its active metabolites. Results The t 1/2 was prolonged with increasing severity of renal impairment. Compared to subjects with normal renal function, patients with mild, moderate and severe renal impairment showed increases in plasma crisugabalin C max by 6.00%, 13.83% and 21.63%, respectively. The AUC 0‐inf of plasma crisugabalin in patients with mild, moderate and severe renal impairment increased by 14.63%, 119.57% and 272.61%, respectively, compared to subjects with normal renal function. Conclusion For patients with GFR < 60 mL/min, dosage adjustments of crisugabalin should be considered. To maintain comparable plasma drug concentrations in patients with impaired renal function, it is recommended that crisugabalin doses be decreased by approximately 50% for every 50% decline in GFR. 10.1002/bcp.70310 http://creativecommons.org/licenses/by-nc/4.0/ |
| doi_str_mv | 10.1002/bcp.70310 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_bcp_70310 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao British Journal of Clinical Pharmacology Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment Shibeilei Lin Ye Wang Chao Hu Yanhuan Feng Xi Tang Ping Fu Jia Miao British Journal of Clinical Pharmacology Aims Crisugabalin is a novel calcium channel α2δ subunit ligand and a highly selective oral gamma‐aminobutyric acid (GABA) analogue developed for the treatment of diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). This study investigated pharmacokinetic properties and safety of crisugabalin in subjects with renal impairment. Methods This multicenter, nonrandomized, open‐label Phase I study investigated the pharmacokinetics and safety of a single oral 20‐mg dose of crisugabalin capsule in Chinese subjects with various degrees of renal function, categorized according to the absolute glomerular filtration rate (GFR). A total of 32 subjects (eight subjects per renal function category [normal, mild, moderate, or severe impairment]) were enrolled and completed the study. Blood samples were collected up to 72 h post‐dose, along with fractionated urine samples. Active moiety exposures were calculated as the sum of unbound exposures for crisugabalin and its active metabolites. Results The t 1/2 was prolonged with increasing severity of renal impairment. Compared to subjects with normal renal function, patients with mild, moderate and severe renal impairment showed increases in plasma crisugabalin C max by 6.00%, 13.83% and 21.63%, respectively. The AUC 0‐inf of plasma crisugabalin in patients with mild, moderate and severe renal impairment increased by 14.63%, 119.57% and 272.61%, respectively, compared to subjects with normal renal function. Conclusion For patients with GFR < 60 mL/min, dosage adjustments of crisugabalin should be considered. To maintain comparable plasma drug concentrations in patients with impaired renal function, it is recommended that crisugabalin doses be decreased by approximately 50% for every 50% decline in GFR. 10.1002/bcp.70310 http://creativecommons.org/licenses/by-nc/4.0/ |
| title | Safety and pharmacokinetics of a novel potent GABA analogue crisugabalin in Chinese subjects with various degrees of renal impairment |
| topic | British Journal of Clinical Pharmacology |
| url | https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/bcp.70310 |