{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T17:15:44Z","timestamp":1697562944896},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,7,7]],"date-time":"2008-07-07T00:00:00Z","timestamp":1215388800000},"content-version":"vor","delay-in-days":2744,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:p><jats:bold>Aims\u2002<\/jats:bold> To assess the pharmacodynamics of moxonidine in patients with functional NYHA Class II\u2010III congestive heart failure (CHF).<\/jats:p><jats:p><jats:bold>Methods\u2002<\/jats:bold> A parallel population pharmacokinetic\/pharmacodynamic (PK\/PD) analysis was performed to assess the effect of moxonidine (0.1, 0.2, 0.3\u2003mg twice daily) and placebo treatment on plasma noradrenaline (NA) levels, standing systolic blood pressure (SBP), and heart rate (HR) over 12\u2003weeks in 97 patients with CHF using a parallel group design with dose escalation. A sequential analysis was also developed, where the relative changes in NA concentration were related to both SBP and HR.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> In the parallel PD analysis, an effect delay was shown for all three end points (NA, SBP, and HR). An inhibitory E<jats:sub>max<\/jats:sub> model was used to characterize the concentration\u2010effect relationships. For SBP and HR, the E<jats:italic>C<\/jats:italic><jats:sub>50<\/jats:sub> value increased over time. For NA, there was a positive baseline drift over the 12\u2003weeks; this was interpreted as disease progression. Moxonidine delayed this increase by 9.8\u2003weeks. For SBP, there was a circadian pattern at baseline. In the sequential PD analysis, the relationship between the drug response (NA) and SBP or HR was best described by an inhibitory E<jats:sub>max<\/jats:sub> model. No effect delays between the response and effects were found.<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> Effects of moxonidine on NA, SBP, and HR could be quantified by an effect compartment model in the presence of disease progression and circadian variations. Disease progression, as judged by increasing NA levels with time, was delayed by moxonidine. A direct relationship was found between NA and SBP\/HR.<\/jats:p>","DOI":"10.1046\/j.1365-2125.2001.01320.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T04:39:57Z","timestamp":1047357597000},"page":"35-43","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacodynamic models for the cardiovascular effects of moxonidine in patients with congestive heart failure"],"prefix":"10.1111","volume":"51","author":[{"given":"Lena","family":"Brynne","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"McNay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans G.","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curtis G.","family":"Wiltse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats O.","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,7]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198606123142404"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198409273111303"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(82)90243-0"},{"key":"e_1_2_5_7_2","first-page":"VI","article-title":"Plasma norepinephrine, plasmarenin\u2010activity and congestive heart failure. 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