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‐...
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| Published in: | Journal of clinical pharmacology Vol. 64; no. 11; pp. 1361 - 1372 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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01.11.2024
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| ISSN: | 0091-2700, 1552-4604, 1552-4604 |
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| 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. |
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| 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 |
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| 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 |
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| Keywords | drug interaction epoprostenol pharmacodynamics tolerability pharmacokinetics zamicastat dopamine β‐hydroxylase |
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| 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 |
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| 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,... |
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| 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 |
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