Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet
Lei Sun,1 Sergey Yagoda,2 Yangchun Du,3 Lisa von Moltke21Department of Clinical Pharmacology and Translational Medicine, Alkermes, Inc., Waltham, MA, USA; 2Department of Clinical Research, Alkermes, Inc., Waltham, MA, USA; 3Department of Biostatistics, Alkermes, Inc., Waltham, MA, USACorrespondence:...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-08-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/effect-of-hepatic-and-renal-impairment-on-the-pharmacokinetics-of-olan-peer-reviewed-article-DDDT |
| _version_ | 1819080387769401344 |
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| author | Sun L Yagoda S Du Y von Moltke L |
| author_facet | Sun L Yagoda S Du Y von Moltke L |
| author_sort | Sun L |
| collection | DOAJ |
| description | Lei Sun,1 Sergey Yagoda,2 Yangchun Du,3 Lisa von Moltke21Department of Clinical Pharmacology and Translational Medicine, Alkermes, Inc., Waltham, MA, USA; 2Department of Clinical Research, Alkermes, Inc., Waltham, MA, USA; 3Department of Biostatistics, Alkermes, Inc., Waltham, MA, USACorrespondence: Lei SunClinical Pharmacology and Translational Medicine, Alkermes, Inc., 852 Winter Street, Waltham, MA 02451, USATel +1 781 609 6151Fax +1 781 609 5851Email lei.sun@alkermes.comBackground: A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain.Methods: Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7–9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate: 15–29 mL/min/1.73 m2,; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg.Results: There was a 1.67-fold increase in area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) and a 2.17-fold increase in maximum plasma concentration (Cmax) of olanzapine, and a 1.52-fold increase in AUC0-∞ and a 1.63-fold increase in Cmax of samidorphan, in subjects with moderate hepatic impairment compared with healthy control subjects. Compared with healthy control subjects, subjects with severe renal impairment had a 33% and 56% reduction in clearance, a 1.51- and 2.31-fold increase in AUC0-∞, and a 1.32- and 1.37-fold increase in Cmax of olanzapine and samidorphan, respectively.Conclusion: OLZ/SAM 5/10 mg was generally well tolerated under the conditions of the studies, with a safety profile consistent with that observed in other clinical studies of OLZ/SAM.Keywords: olanzapine, samidorphan, renal impairment, hepatic impairment, pharmacokinetics
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| first_indexed | 2024-12-21T19:44:05Z |
| format | Article |
| id | doaj.art-5e5464732baa4a5eab665088244574f3 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T19:44:05Z |
| publishDate | 2019-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-5e5464732baa4a5eab665088244574f32022-12-21T18:52:22ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-08-01Volume 132941295548052Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tabletSun LYagoda SDu Yvon Moltke LLei Sun,1 Sergey Yagoda,2 Yangchun Du,3 Lisa von Moltke21Department of Clinical Pharmacology and Translational Medicine, Alkermes, Inc., Waltham, MA, USA; 2Department of Clinical Research, Alkermes, Inc., Waltham, MA, USA; 3Department of Biostatistics, Alkermes, Inc., Waltham, MA, USACorrespondence: Lei SunClinical Pharmacology and Translational Medicine, Alkermes, Inc., 852 Winter Street, Waltham, MA 02451, USATel +1 781 609 6151Fax +1 781 609 5851Email lei.sun@alkermes.comBackground: A combination of olanzapine and samidorphan (OLZ/SAM) is in development to provide the established antipsychotic efficacy of olanzapine while mitigating olanzapine-induced weight gain.Methods: Two multicenter, open-label, parallel-cohort studies were performed to evaluate the effect of moderate hepatic impairment (Child-Pugh score 7–9 [class B]; study 1) and severe renal impairment (estimated glomerular filtration rate: 15–29 mL/min/1.73 m2,; study 2) on the pharmacokinetics, safety, and tolerability of a single dose of OLZ/SAM 5/10 mg.Results: There was a 1.67-fold increase in area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) and a 2.17-fold increase in maximum plasma concentration (Cmax) of olanzapine, and a 1.52-fold increase in AUC0-∞ and a 1.63-fold increase in Cmax of samidorphan, in subjects with moderate hepatic impairment compared with healthy control subjects. Compared with healthy control subjects, subjects with severe renal impairment had a 33% and 56% reduction in clearance, a 1.51- and 2.31-fold increase in AUC0-∞, and a 1.32- and 1.37-fold increase in Cmax of olanzapine and samidorphan, respectively.Conclusion: OLZ/SAM 5/10 mg was generally well tolerated under the conditions of the studies, with a safety profile consistent with that observed in other clinical studies of OLZ/SAM.Keywords: olanzapine, samidorphan, renal impairment, hepatic impairment, pharmacokinetics https://www.dovepress.com/effect-of-hepatic-and-renal-impairment-on-the-pharmacokinetics-of-olan-peer-reviewed-article-DDDTolanzapinesamidorphanrenal impairmenthepatic impairmentpharmacokinetics |
| spellingShingle | Sun L Yagoda S Du Y von Moltke L Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet Drug Design, Development and Therapy olanzapine samidorphan renal impairment hepatic impairment pharmacokinetics |
| title | Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| title_full | Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| title_fullStr | Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| title_full_unstemmed | Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| title_short | Effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| title_sort | effect of hepatic and renal impairment on the pharmacokinetics of olanzapine and samidorphan given in combination as a bilayer tablet |
| topic | olanzapine samidorphan renal impairment hepatic impairment pharmacokinetics |
| url | https://www.dovepress.com/effect-of-hepatic-and-renal-impairment-on-the-pharmacokinetics-of-olan-peer-reviewed-article-DDDT |
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