Abstract：
:Sinbaglustat (ACT-519276), a brain-penetrating inhibitor of glucosylceramide synthase and nonlysosomal glucosylceramidase, is developed as a new therapy for lysosomal storage disorders. In the first-in-human study, sinbaglustat was primarily excreted unchanged in urine. This study was conducted to evaluate the effect of mild, moderate, and severe renal function impairment on the safety, tolerability, and pharmacokinetics (PK) of sinbaglustat. In this single-center, open-label study, 32 subjects (8 per renal function group, assessed by the Cockcroft-Gault formula, and 8 healthy subjects) received a single oral dose of 200 mg sinbaglustat. Plasma PK parameters of sinbaglustat were derived by noncompartmental analysis. Standard safety and tolerability evaluations were analyzed descriptively. When compared with healthy subjects, Cmax did not present clinically relevant differences in subjects with impaired renal function, but median tmax was slightly longer in subjects with moderate and severe renal function impairment. Overall, when compared with healthy subjects, exposure to sinbaglustat based on AUC0-t (geometric mean and 90% confidence interval) increased in subjects with mild, moderate, and severe renal function impairment by 1.2-fold (1.08- to 1.36-fold), 1.8-fold (1.47- to 2.17-fold), and 2.6-fold (2.23- to 3.00-fold), respectively. There were no clinically relevant findings on electrocardiogram, vital signs, and clinical laboratory variables. Headache was reported by 2 of 24 subjects with renal function impairment and by 2 of 8 healthy subjects. In conclusion, 200 mg of sinbaglustat was well tolerated in all groups. In future studies, a 2- and 3-fold dose reduction is needed for subjects with moderate and severe renal function impairment, respectively.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Melchior M,Dingemanse J,Alatrach A,Feldkamp T,Sidharta PN,Géhin Mdoi
10.1002/jcph.1808subject
Has Abstractpub_date
2020-12-23 00:00:00eissn
0091-2700issn
1552-4604pub_type
杂志文章abstract：:To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent...
journal_title：Journal of clinical pharmacology
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abstract：:The clinical pharmacist is an integral member of the Docent team at the University of Missouri--Kansas City School of Medicine with duties in both teaching and patient care. These doctoral-level clinical pharmacists have sole responsibility for providing instruction in basic pharmacology and pharmacokinetics and for t...
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journal_title：Journal of clinical pharmacology
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pub_type： 杂志文章,多中心研究,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1991-08-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007307243
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-12-01 00:00:00
abstract：:The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 he...
journal_title：Journal of clinical pharmacology
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更新日期：2010-03-01 00:00:00
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doi：10.1002/j.1552-4604.1993.tb04668.x
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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abstract：:UCN-01 is a protein kinase inhibitor under development as a novel anticancer drug. The initial pharmacologic features in patients were not predicted from preclinical experiments. The distribution volume and the systemic clearance were much lower than those in experimental animals (mice, rats, and dogs), and the elimin...
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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abstract：:Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing alpha- and beta-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) inve...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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