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British Journal of Clinical Pharmacology
Article . 2022 . Peer-reviewed
License: CC BY NC ND
Data sources: Crossref
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Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam

Authors: Heidemarie Kletzl; Hassan Ajmi; Izabela Antys; Katja Heinig; Birgit Jaber; Thomas C. Marbury; Annie Young; +1 Authors

Effect of mild or moderate hepatic impairment on the pharmacokinetics of risdiplam

Abstract

AimThis phase I, multicentre, open‐label, nonrandomised, parallel‐group, two‐part study aimed to evaluate the effect of mild to moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of risdiplam.MethodsAdult subjects (aged 18‐70 years) with mild (Child‐Pugh Class A; Part 1) or moderate (Child‐Pugh Class B; Part 2) hepatic impairment were matched with subjects with normal hepatic function on sex, age, body mass index and smoking status. Each subject received a single oral dose of 5 mg of risdiplam. Plasma concentrations of risdiplam and its metabolite M1 were measured and PK parameters were compared. Adverse events, laboratory abnormalities, vital signs and electrocardiogram measurements were assessed.ResultsAfter a single dose (5 mg) of risdiplam, the risdiplam PK parameters area under the plasma concentration‐time curve from time zero to infinity and maximum observed plasma concentration were approximately 20% and 5% lower, respectively, in subjects with mild hepatic impairment and approximately 8% and 20% higher, respectively, in subjects with moderate hepatic impairment compared with subjects with normal hepatic function. These differences were not statistically significant; all 90% confidence intervals for geometric least squares‐means ratios spanned unity. No new risdiplam‐related safety findings were observed in subjects with mild or moderate hepatic impairment.ConclusionMild or moderate hepatic impairment did not have a clinically relevant impact on the PK of risdiplam. Therefore, no dose adjustment is required in patients with mild or moderate hepatic impairment when receiving risdiplam.

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Keywords

Adult, Male, Adolescent, Liver Diseases, Original Articles, Middle Aged, Pyrimidines, Area Under Curve, Humans, Female, Azo Compounds, Aged

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Top 10%
Average
Top 10%
Green
hybrid