Drug‐Drug Interaction between Oral Zamicastat and Continuous Epoprostenol Infusion at Steady‐State Conditions in Healthy Subjects
This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐...
Uloženo v:
| Vydáno v: | Journal of clinical pharmacology Ročník 64; číslo 11; s. 1361 - 1372 |
|---|---|
| Hlavní autoři: | , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
England
Wiley Subscription Services, Inc
01.11.2024
|
| Témata: | |
| ISSN: | 0091-2700, 1552-4604, 1552-4604 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC0‐16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0‐τ,ss, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0‐τ,ss and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0‐τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. |
|---|---|
| AbstractList | This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for C
av,ss
and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC
0‐16,ss
) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC
0‐τ,ss
, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat C
max,ss
, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, C
max,ss
and AUC
0‐τ,ss
and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for C
max,ss
and between 21% and 41% for AUC
0‐τ,ss
, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label, two-period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8-day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat-to-epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for C and area under the plasma concentration-time curve from time 0 up to 16 h at steady state (AUC ) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%-125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC , the zamicastat plus epoprostenol-to-zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat C , the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, C and AUC and the zamicastat plus epoprostenol-to-zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for C and between 21% and 41% for AUC , for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label, two-period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8-day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat-to-epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration-time curve from time 0 up to 16 h at steady state (AUC0-16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%-125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0-τ,ss, the zamicastat plus epoprostenol-to-zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0-τ,ss and the zamicastat plus epoprostenol-to-zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0-τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant.This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label, two-period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8-day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat-to-epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration-time curve from time 0 up to 16 h at steady state (AUC0-16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%-125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0-τ,ss, the zamicastat plus epoprostenol-to-zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0-τ,ss and the zamicastat plus epoprostenol-to-zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0-τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label, two‐period study. In period 1, epoprostenol 8 ng/kg/min was administered alone. In period 2, epoprostenol 8 ng/kg/min was administered following an 8‐day treatment with zamicastat. Since the initial dose of epoprostenol showed to be insufficiently tolerated, it was decreased to 6 ng/kg/min. Blood samples were collected to determine the metabolites of epoprostenol and concentrations of zamicastat and its metabolites. A total of 54 subjects were enrolled and data from 28 subjects were available for pharmacokinetic analysis. The epoprostenol plus zamicastat‐to‐epoprostenol geometric means ratio (GMR) and corresponding 90% confidence interval (CI) for Cav,ss and area under the plasma concentration–time curve from time 0 up to 16 h at steady state (AUC0‐16,ss) of the metabolites of epoprostenol were within the acceptance bioequivalence range (80.00%‐125.00%). The intrasubject coefficient of variation (ISCV) was below 10% for both parameters, on both metabolites. For zamicastat AUC0‐τ,ss, the zamicastat plus epoprostenol‐to‐zamicastat GMR and corresponding 90% CI were within the bioequivalence acceptance range, while for zamicastat Cmax,ss, the lower limit of the 90% CI was slightly below the acceptance range. For zamicastat metabolites, Cmax,ss and AUC0‐τ,ss and the zamicastat plus epoprostenol‐to‐zamicastat GMR were below the acceptance bioequivalence range. ISCV was between 30% and 41% for Cmax,ss and between 21% and 41% for AUC0‐τ,ss, for zamicastat and both metabolites. This study showed that the administration of zamicastat did not significantly modify the cardiovascular effects of epoprostenol and that the interactions between zamicastat and epoprostenol are not expected to be clinically relevant. |
| Author | Guimarães, Andreia Gama, Helena Fonseca, Marlene Magalhães, Luís Silva, Nuno Soares‐da‐Silva, Patrício Henriques, Sara Carolina Almeida, Luis |
| Author_xml | – sequence: 1 givenname: Marlene orcidid: 0009-0000-5828-8535 surname: Fonseca fullname: Fonseca, Marlene email: mfonseca@blueclinical.pt organization: BlueClinical Phase I – sequence: 2 givenname: Andreia surname: Guimarães fullname: Guimarães, Andreia organization: Bial‐Portela & Cª S.A., Coronado (S. Romao e S. Mamede) – sequence: 3 givenname: Helena surname: Gama fullname: Gama, Helena organization: Bial‐Portela & Cª S.A., Coronado (S. Romao e S. Mamede) – sequence: 4 givenname: Luís surname: Magalhães fullname: Magalhães, Luís organization: Bial‐Portela & Cª S.A., Coronado (S. Romao e S. Mamede) – sequence: 5 givenname: Sara Carolina orcidid: 0000-0001-9649-4823 surname: Henriques fullname: Henriques, Sara Carolina organization: University of Lisbon – sequence: 6 givenname: Nuno surname: Silva fullname: Silva, Nuno organization: University of Lisbon – sequence: 7 givenname: Luis surname: Almeida fullname: Almeida, Luis organization: University of Porto – sequence: 8 givenname: Patrício surname: Soares‐da‐Silva fullname: Soares‐da‐Silva, Patrício organization: University of Porto |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38924604$$D View this record in MEDLINE/PubMed |
| BookMark | eNp10TtvFDEQB3ALBZFLoOALIEs0pNhk_NhXiS6BC4oUpIOGxpq1Z8me9rzH2qvoOhr6fEY-CV4uUCBRTfP7j-Zxwo784ImxlwLOBYC82Njd3bnUVfGELUSey0wXoI_YAqAWmSwBjtlJCBsAUehcPGPHqqrlbBbsx-U4ff35_WEu_NpHGtHGbvC8oXhP5PntiD3_gtvOYogYOXrHl4OPnZ-GKfCr3bAbhxDJD33Kt1OYw8mtI6Hbp87rlKI54rq5ceCd5yvCPt7t-XpqNmRjeM6ettgHevFYT9nnd1eflqvs5vb99fLtTWaVUEVmLeSoW10rVdROyYoE5FZgWTZVVUqrsHGurXNXUVKgSyw1NK1C5wrXYqtO2ZtD3zTzt4lCNNsuWOp79JS2MQpKWdZ1pVWir_-hm2EafZrOKCEhT-fO66RePaqp2ZIzu7Hb4rg3fw6cwNkB2HSlMFL7lwgw8_PM_DwzPy_Zi4O973ra_x-aD8uPq9-JX2zhnsw |
| Cites_doi | 10.1164/ajrccm‐conference.2020.201.1_MeetingAbstracts.A3816 10.3390/diseases6020038 10.1007/s40256‐018‐0272‐5 10.1186/s13019‐022‐01947‐y 10.1111/j.1365‐2125.2012.04301.x 10.1016/j.chest.2021.07.2010 10.1038/clpt.1981.58 10.1517/17425255.2010.534458 10.1016/j.clinthera.2013.02.013 10.1161/01.cir.102.8.865 10.1093/eurheartj/ehac237 10.1378/chest.09‐1140 10.1183/09031936.00092306 10.1016/j.ejphar.2014.07.027 10.1183/09031936.00145708 10.1136/bmj.j5492 10.1038/sj.bjp.0701315 10.1161/circ.142.suppl_3.14740 10.1096/fasebj.2020.34.s1.05359 10.1183/16000617.0055‐2016 10.1161/01.CIR.0000140724.90898.D3 |
| ContentType | Journal Article |
| Copyright | 2024, The American College of Clinical Pharmacology. |
| Copyright_xml | – notice: 2024, The American College of Clinical Pharmacology. |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QP 7QR 7T5 7TK 7TM 8FD FR3 H94 K9. NAPCQ P64 RC3 7X8 |
| DOI | 10.1002/jcph.2486 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Technology Research Database Engineering Research Database AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Nursing & Allied Health Premium Genetics Abstracts Technology Research Database Nucleic Acids Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Chemoreception Abstracts Immunology Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
| DatabaseTitleList | CrossRef MEDLINE MEDLINE - Academic Nursing & Allied Health Premium |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1552-4604 |
| EndPage | 1372 |
| ExternalDocumentID | 38924604 10_1002_jcph_2486 JCPH2486 |
| Genre | article Clinical Trial Journal Article |
| GroupedDBID | --- .55 .GJ 05W 0R~ 123 18M 1CY 1OB 1OC 29K 33P 34G 39C 3O- 3SF 4.4 52U 52V 53G 5RE 8-1 A00 AAESR AAEVG AAHHS AAHQN AAIPD AAMNL AANHP AANLZ AAONW AASGY AAWTL AAXRX AAYCA AAYOK AAZKR ABCUV ABJNI ABQWH ABXGK ACAHQ ACBWZ ACCFJ ACCZN ACGFO ACGFS ACGOF ACIWK ACMXC ACPOU ACPRK ACRPL ACXBN ACXME ACXQS ACYXJ ADBBV ADBTR ADEOM ADIZJ ADMGS ADNMO ADOZA ADXAS AEEZP AEGXH AEIGN AEIMD AENEX AEQDE AEUYR AFBPY AFFNX AFFPM AFGKR AFPWT AFRAH AFWVQ AHBTC AHMBA AI. AIACR AIAGR AITYG AIURR AIWBW AJBDE ALMA_UNASSIGNED_HOLDINGS ALUQN ALVPJ AMBMR AMYDB ASPBG ATUGU AUVAJ AVWKF AZFZN AZVAB BDRZF BFHJK BHBCM BMXJE BOGZA BRXPI C45 CAG COF CS3 D-I DCZOG DPXWK DRFUL DRMAN DRSTM DU5 EBD EBS EJD EMOBN F5P FEDTE FUBAC G-S GODZA GWYGA H13 HF~ HGLYW HVGLF IAO IEA IHR INH INR IVC KBYEO LATKE LEEKS LH4 LOXES LSO LUTES LW6 LYRES M4V MEWTI MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM MY~ N9A O66 O9- OVD P2P P2W PALCI PQQKQ R.K RIWAO RJQFR ROL SAMSI SUPJJ SV3 TEORI VH1 WBKPD WH7 WIH WIJ WIK WOHZO WOIKV WPGGZ WXSBR WYJ X7M YCJ ZGI ZXP ZZTAW AAMMB AAYXX ADSTG AEFGJ AEYWJ AGHNM AGQPQ AGXDD AGYGG AIDQK AIDYY AIQQE CITATION CGR CUY CVF ECM EIF NPM 7QP 7QR 7T5 7TK 7TM 8FD FR3 H94 K9. NAPCQ P64 RC3 7X8 |
| ID | FETCH-LOGICAL-c3136-cc05a4f493369d328e105c1a77b8872c3abddf95d8e4f4047a740bf3add6dfaf3 |
| IEDL.DBID | DRFUL |
| ISICitedReferencesCount | 0 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001253909500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0091-2700 1552-4604 |
| IngestDate | Sun Nov 09 14:27:56 EST 2025 Mon Oct 06 18:02:52 EDT 2025 Wed Feb 19 02:04:03 EST 2025 Sat Nov 29 03:59:39 EST 2025 Wed Jan 22 17:15:36 EST 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 11 |
| Keywords | drug interaction epoprostenol pharmacodynamics tolerability pharmacokinetics zamicastat dopamine β‐hydroxylase |
| Language | English |
| License | 2024, The American College of Clinical Pharmacology. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c3136-cc05a4f493369d328e105c1a77b8872c3abddf95d8e4f4047a740bf3add6dfaf3 |
| Notes | Clinical Trial Registration: EudraCT No. 2020‐000224‐18 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0009-0000-5828-8535 0000-0001-9649-4823 |
| PMID | 38924604 |
| PQID | 3120524859 |
| PQPubID | 37812 |
| PageCount | 12 |
| ParticipantIDs | proquest_miscellaneous_3072799843 proquest_journals_3120524859 pubmed_primary_38924604 crossref_primary_10_1002_jcph_2486 wiley_primary_10_1002_jcph_2486_JCPH2486 |
| PublicationCentury | 2000 |
| PublicationDate | November 2024 2024-11-00 2024-Nov 20241101 |
| PublicationDateYYYYMMDD | 2024-11-01 |
| PublicationDate_xml | – month: 11 year: 2024 text: November 2024 |
| PublicationDecade | 2020 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England – name: Rockville |
| PublicationTitle | Journal of clinical pharmacology |
| PublicationTitleAlternate | J Clin Pharmacol |
| PublicationYear | 2024 |
| Publisher | Wiley Subscription Services, Inc |
| Publisher_xml | – name: Wiley Subscription Services, Inc |
| References | 2018; 360 2017; 26 2012 2020; 142 2021; 160 1981; 29 2020; 34 2022; 43 2007; 30 2020; 201 2024 2012; 74 2009; 34 2018; 6 2018; 18 2004; 110 2000; 102 2022 2013; 35 2020 2010; 137 1997; 121 2022; 17 2010; 6 2014; 740 e_1_2_11_10_1 Patel N (e_1_2_11_28_1) 2024 e_1_2_11_14_1 e_1_2_11_13_1 e_1_2_11_12_1 e_1_2_11_11_1 e_1_2_11_7_1 e_1_2_11_6_1 e_1_2_11_5_1 e_1_2_11_27_1 e_1_2_11_4_1 e_1_2_11_26_1 e_1_2_11_3_1 e_1_2_11_2_1 e_1_2_11_21_1 e_1_2_11_20_1 e_1_2_11_25_1 e_1_2_11_24_1 e_1_2_11_9_1 e_1_2_11_23_1 e_1_2_11_8_1 e_1_2_11_22_1 e_1_2_11_18_1 e_1_2_11_17_1 e_1_2_11_16_1 e_1_2_11_15_1 e_1_2_11_19_1 |
| References_xml | – volume: 74 start-page: 978 issue: 6 year: 2012 end-page: 989 article-title: Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects publication-title: Br J Clin Pharmacol – volume: 30 start-page: 104 issue: 1 year: 2007 end-page: 109 article-title: An epidemiological study of pulmonary arterial hypertension publication-title: Eur Respir J – volume: 102 start-page: 865 issue: 8 year: 2000 end-page: 870 article-title: Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension publication-title: Circulation – volume: 34 start-page: 895 issue: 4 year: 2009 end-page: 901 article-title: Impaired cardiac autonomic control relates to disease severity in pulmonary hypertension publication-title: Eur Respir J – volume: 18 start-page: 249 issue: 4 year: 2018 end-page: 257 article-title: Pulmonary arterial hypertension: combination therapy in practice publication-title: Am J Cardiovasc Drugs – year: 2024 – volume: 6 start-page: 38 issue: 2 year: 2018 article-title: Pulmonary arterial hypertension: pathophysiology and treatment publication-title: Diseases – volume: 6 start-page: 1587 issue: 12 year: 2010 end-page: 1598 article-title: Pharmacokinetic evaluation of continuous intravenous epoprostenol publication-title: Expert Opin Drug Metab Toxicol – volume: 360 year: 2018 article-title: Pulmonary arterial hypertension: pathogenesis and clinical management publication-title: BMJ – volume: 201 start-page: A3816 year: 2020 end-page: A3816 article-title: A double‐blind, randomised, placebo‐controlled, multiple ascending dose study to investigate safety, tolerability, pharmacokinetic and pharmacodynamic profile of zamicastat, in healthy male volunteers. In: B56. Pulmonary Hypertension Clinical Trials Endeavor Safety, Combination What Else? publication-title: American Thoracic Society – volume: 121 start-page: 1803 issue: 8 year: 1997 end-page: 1809 article-title: Catecholamine modulatory effects of nepicastat (RS‐25560‐197), a novel, potent and selective inhibitor of dopamine‐beta‐hydroxylase publication-title: Br J Pharmacol – year: 2012 – volume: 29 start-page: 420 issue: 3 year: 1981 end-page: 424 article-title: Prostacyclin metabolites in human plasma publication-title: Clin Pharmacol Ther – volume: 110 start-page: 1308 issue: 10 year: 2004 end-page: 1312 article-title: Increased sympathetic nerve activity in pulmonary artery hypertension publication-title: Circulation – volume: 26 issue: 143 year: 2017 article-title: Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience publication-title: Eur Respir Rev – volume: 137 start-page: 376 issue: 2 year: 2010 end-page: 387 article-title: Pulmonary arterial hypertension publication-title: Chest – volume: 34 start-page: 1 issue: S1 year: 2020 article-title: Zamicastat is a noncompetitive dopamine‐β‐hydroxylase inhibitor that modulates sympathetic nervous system activity publication-title: Faseb J – year: 2022 article-title: ICH guideline M10 on bioanalytical method validation and study sample analysis – volume: 740 start-page: 285 year: 2014 end-page: 294 article-title: Etamicastat, a new dopamine‐ss‐hydroxylase inhibitor, pharmacodynamics and metabolism in rat publication-title: Eur J Pharmacol – volume: 17 start-page: 216 issue: 1 year: 2022 article-title: New progress in diagnosis and treatment of pulmonary arterial hypertension publication-title: J Cardiothorac Surg – year: 2022 – volume: 160 start-page: A2309 issue: 4 year: 2021 end-page: A2310 article-title: An integrated assessment of pharmacokinetics and pharmacodynamics of zamicastat: a dopamine β‐hydroxylase inhibitor in healthy volunteers publication-title: Chest – volume: 142 year: 2020 article-title: Sympathetic down‐regulation with zamicastat reduces arrhythmogenicity in isolated hearts from rats with pulmonary hypertension publication-title: Circulation – year: 2020 – volume: 43 start-page: 3618 issue: 38 year: 2022 end-page: 3731 article-title: 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension publication-title: Eur Heart J – volume: 35 start-page: 440 issue: 4 year: 2013 end-page: 449 article-title: Comparative pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of 3 different formulations of epoprostenol sodium for injection in healthy men publication-title: Clin Ther – ident: e_1_2_11_22_1 doi: 10.1164/ajrccm‐conference.2020.201.1_MeetingAbstracts.A3816 – ident: e_1_2_11_13_1 – volume-title: Physiology, Cardiac Index year: 2024 ident: e_1_2_11_28_1 – ident: e_1_2_11_5_1 doi: 10.3390/diseases6020038 – ident: e_1_2_11_6_1 doi: 10.1007/s40256‐018‐0272‐5 – ident: e_1_2_11_7_1 doi: 10.1186/s13019‐022‐01947‐y – ident: e_1_2_11_9_1 doi: 10.1111/j.1365‐2125.2012.04301.x – ident: e_1_2_11_24_1 – ident: e_1_2_11_26_1 doi: 10.1016/j.chest.2021.07.2010 – ident: e_1_2_11_14_1 doi: 10.1038/clpt.1981.58 – ident: e_1_2_11_25_1 doi: 10.1517/17425255.2010.534458 – ident: e_1_2_11_10_1 doi: 10.1016/j.clinthera.2013.02.013 – ident: e_1_2_11_17_1 doi: 10.1161/01.cir.102.8.865 – ident: e_1_2_11_8_1 doi: 10.1093/eurheartj/ehac237 – ident: e_1_2_11_2_1 doi: 10.1378/chest.09‐1140 – ident: e_1_2_11_3_1 doi: 10.1183/09031936.00092306 – ident: e_1_2_11_12_1 – ident: e_1_2_11_15_1 doi: 10.1016/j.ejphar.2014.07.027 – ident: e_1_2_11_27_1 – ident: e_1_2_11_18_1 doi: 10.1183/09031936.00145708 – ident: e_1_2_11_4_1 doi: 10.1136/bmj.j5492 – ident: e_1_2_11_16_1 doi: 10.1038/sj.bjp.0701315 – ident: e_1_2_11_20_1 doi: 10.1161/circ.142.suppl_3.14740 – ident: e_1_2_11_21_1 doi: 10.1096/fasebj.2020.34.s1.05359 – ident: e_1_2_11_23_1 – ident: e_1_2_11_11_1 doi: 10.1183/16000617.0055‐2016 – ident: e_1_2_11_19_1 doi: 10.1161/01.CIR.0000140724.90898.D3 |
| SSID | ssj0016451 |
| Score | 2.4317727 |
| Snippet | This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single‐center, open‐label,... This study intended to evaluate the interactions between zamicastat and epoprostenol in healthy human subjects. This was a single-center, open-label,... |
| SourceID | proquest pubmed crossref wiley |
| SourceType | Aggregation Database Index Database Publisher |
| StartPage | 1361 |
| SubjectTerms | Administration, Oral Adult Antihypertensive Agents - administration & dosage Antihypertensive Agents - blood Antihypertensive Agents - pharmacokinetics Area Under Curve Bioequivalence dopamine β‐hydroxylase Drug interaction Drug Interactions epoprostenol Epoprostenol - administration & dosage Epoprostenol - pharmacokinetics Female Healthy Volunteers Humans Infusions, Intravenous Male Metabolites Middle Aged pharmacodynamics Pharmacokinetics Prostacyclin Therapeutic Equivalency tolerability Young Adult zamicastat |
| Title | Drug‐Drug Interaction between Oral Zamicastat and Continuous Epoprostenol Infusion at Steady‐State Conditions in Healthy Subjects |
| URI | https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fjcph.2486 https://www.ncbi.nlm.nih.gov/pubmed/38924604 https://www.proquest.com/docview/3120524859 https://www.proquest.com/docview/3072799843 |
| Volume | 64 |
| WOSCitedRecordID | wos001253909500001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVWIB databaseName: Wiley Online Library Full Collection 2020 customDbUrl: eissn: 1552-4604 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0016451 issn: 0091-2700 databaseCode: DRFUL dateStart: 19970101 isFulltext: true titleUrlDefault: https://onlinelibrary.wiley.com providerName: Wiley-Blackwell |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1La9wwEB6STQ-99P1wmwa1lNBDnHgl-UVPJckSSkmXksDSi9HL7ZbiXdZxYW-55N7fmF-SGcvrJZRCoQdjg_Uwkkb6PNL3DcBbY7TIYxeHDtFyiPjfhjoty9A6tCWNK4zjPthEenqaTSb5eAPer7gwXh-id7iRZbTzNRm40vXBWjT0h5l_3-cySzZhi-O4jQewdfRldP6p30RIZOwD5uVDol1FK2GhiB_0mW8vR39gzNuQtV1zRvf_62sfwL0OarIPfmw8hA1XPYLdsdeqXu6xszX1qt5ju2y8VrFePoaro0Xz7fryN91Y6zf0FAjWnexinxdY-FcKZ6-IlcRUZRlpXU2rZtbU7Hg-mxOjxFWzn5i_bMgtxzAdnSC2Syy5xbmUxfpjY2xaMc-KWjKcz8hBVD-B89Hx2eFJ2MVsCI0YiiQ0JoqVLGUuRJJbwTOHAM4MVZpqnM64EUpbW-axzRymimSqUhnpUiiKbFWqUjyFQTWr3HNg3EbKSo2IURspEdgImxGpKCljvDIVwJtV1xVzL81ReBFmXlBzF9TcAWyvOrXorLMuxJBHMWm55QG87l-jXdFmiaoctlKBcx9P8V9UigCe-cHQ14Igj8skkgG8a_v879UXHw_HJ_Tw4t-TvoS7HJGTJzxuw-Bi0bhXcMf8upjWix3YTCfZTjfUbwAS4gav |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3Pa9RAFH7UVtBL62-jVUeR4qGx2ZnJL_AibZdV13WRLZRewmRmoislu2waYW9eevdv9C_xvUw2SxFB8BASyEwmzLw38-Vlvu8BvNQ6F2loQ98iWvYR_xs_j4vCNxZ9KccVxnKXbCIejZLT03S8AW9WXBinD9EF3MgzmvmaHJwC0gdr1dBvev71NZdJdA22JJoR2vfW0ef-ybD7ixDJ0GXMS3vEuwpWykIBP-gqX12P_gCZVzFrs-j0d_7vdW_Bdgs22VtnHbdhw5Z3YG_s1KqX-2yyJl9V-2yPjdc61su7cHm0qL_8-vGTTqyJHDoSBGv3drFPC3z4GSW0V8RLYqo0jNSupmU9qyt2PJ_NiVNiy9k51i9qCswxLEd7iM0Sn9wgXapi3MYxNi2Z40UtGc5oFCKq7sFJ_3hyOPDbrA2-Fj0R-VoHoZKFTIWIUiN4YhHC6Z6K4xwnNK6Fyo0p0tAkFksFMlaxDPJCKMptVahC3IfNclbah8C4CZSROWLGXEuJ0EaYhGhFURHikSgPXqzGLps7cY7MyTDzjLo7o-72YHc1qlnrn1UmejwISc0t9eB5dxs9i36XqNJiL2U4-_EYv0al8OCBs4auFYR5XEaB9OBVM-h_bz57fzge0MWjfy_6DG4MJh-H2fDd6MNjuMkRRzn64y5sXixq-wSu6-8X02rxtLX434XUCbc |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1bi9QwFD6ssyK-eL9UV40iiw9bt5OkN_BFdnZYdRmL7MLiS0mTVEekU6ZbYd588d3f6C_xnKbTYRFB8KG00FxKkpN8Pcn3HYDnWhciDW3oW0TLPuJ_4xdxWfrGoi0VuMJY7oJNxLNZcnaWZlvwas2FcfoQg8ONLKObr8nAbW3K_Y1q6Bddf37JZRJdgm1JQWRGsD35MD09HnYRIhm6iHnpmHhXwVpZKOD7Q-aL69EfIPMiZu0Wnen1__vcG3CtB5vstRsdN2HLVrdgN3Nq1as9drIhXzV7bJdlGx3r1W34MVm2n359_0k31nkOHQmC9We72PslFv6RAtor4iUxVRlGalfzql20DTusFzVxSmy1-Ir5y5YccwzT0Rlis8KSO6RLWYw7OMbmFXO8qBXDGY1cRM0dOJ0enhwc-X3UBl-LsYh8rYNQyVKmQkSpETyxCOH0WMVxgRMa10IVxpRpaBKLqQIZq1gGRSkUxbYqVSnuwqhaVPY-MG4CZWSBmLHQUiK0ESYhWlFUhnglyoNn677LayfOkTsZZp5Tc-fU3B7srHs17-2zycWYByGpuaUePB1eo2XRdomqLLZSjrMfj_FvVAoP7rnRMNSCMI_LKJAevOg6_e_V528PsiN6ePDvSZ_AlWwyzY_fzN49hKscYZRjP-7A6HzZ2kdwWX87nzfLx_2A_w0F5gky |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Drug%E2%80%90Drug+Interaction+between+Oral+Zamicastat+and+Continuous+Epoprostenol+Infusion+at+Steady%E2%80%90State+Conditions+in+Healthy+Subjects&rft.jtitle=Journal+of+clinical+pharmacology&rft.au=Fonseca%2C+Marlene&rft.au=Guimar%C3%A3es%2C+Andreia&rft.au=Gama%2C+Helena&rft.au=Magalh%C3%A3es%2C+Lu%C3%ADs&rft.date=2024-11-01&rft.pub=Wiley+Subscription+Services%2C+Inc&rft.issn=0091-2700&rft.eissn=1552-4604&rft.volume=64&rft.issue=11&rft.spage=1361&rft.epage=1372&rft_id=info:doi/10.1002%2Fjcph.2486&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0091-2700&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0091-2700&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0091-2700&client=summon |