{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:13:06Z","timestamp":1776769986885,"version":"3.51.2"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Poor statin adherence remains a public health concern associated with adverse outcomes. We evaluated the use of pharmacokinetic measurements to monitor adherence to simvastatin in patients with coronary heart disease (CHD).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Eighteen patients with CHD taking an evening dose of simvastatin 20 mg (n = 7), 40 mg (n = 5), or 80 mg (n = 6) were examined at steady-state pharmacokinetics. Ten patients were instructed to interrupt simvastatin dosing and return for blood sampling for the subsequent 3 days. Dose-normalized plasma concentrations of simvastatin lactone and simvastatin acid and the sum of the 2 were evaluated to discriminate between adherent dosing and dose omission. Bioanalytical quantification was performed using liquid chromatography\u2013tandem mass spectrometry.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>A simvastatin acid cutoff of 1.0 \u00d7 10<jats:sup>\u22122<\/jats:sup> nmol<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup>\u00b7mg<jats:sup>\u22121<\/jats:sup> identified 100% of those omitting 2 doses and 60% of those omitting a single dose. Simvastatin acid showed superior ability to discriminate dose omission, as well as the best agreement between samples handled at ambient and cool temperatures (median deviation 3.5%; interquartile range \u22122.5% to 13%). The cutoff for a morning dose schedule, with a similar ability to discriminate, was estimated at 2.0 \u00d7 10<jats:sup>\u22123<\/jats:sup> nmol<jats:sup>\u22121<\/jats:sup>\u00b7L<jats:sup>\u22121<\/jats:sup>\u00b7mg<jats:sup>\u22121<\/jats:sup>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The present method discriminated between adherence and reduced adherence to simvastatin therapy in patients with CHD. Sample handling is feasible for routine practice, and the assessment of adherence can be performed by direct measurement of simvastatin acid in a blood sample, according to defined cutoff values. Further studies validating the cutoff value and utility for clinical application are encouraged.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000992","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T17:05:50Z","timestamp":1651165550000},"page":"558-567","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["Monitoring Simvastatin Adherence in Patients With Coronary Heart Disease: A Proof-of-Concept Study Based on Pharmacokinetic Measurements in Blood Plasma"],"prefix":"10.1097","volume":"44","author":[{"given":"Nils Tore","family":"Vethe","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Oslo University Hospital, Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Einar","family":"Husebye","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders M.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Oslo University Hospital, Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stein","family":"Bergan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Oslo University Hospital, Oslo;"},{"name":"Department of Pharmacy, University of Oslo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Kristiansen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen;"},{"name":"Department of Behavioural Medicine, Faculty of Medicine, University of Oslo; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten W.","family":"Fagerland","sequence":"additional","affiliation":[{"name":"Oslo Centre for Biostatistics and Epidemiology; Joint Centre between the Section of 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