Mimi Stokke Opdal

• Havig, Stine Marie; Berg-Pedersen, Riikka Mari; Krabseth, Hege-Merete; Müller, Lill Dannevig; Haugaa, Kristina Ingrid Helena Hermann & Zare, Hasse Khiabani [Vis alle 9 forfattere av denne artikkelen] (2024). Effect on QTc interval by switching from methadone to equipotent R-methadone dose in methadone maintenance treatment patients. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. doi: 10.1111/bcpt.13982.
• Halvorsen, Lene Vernås; Bergland, Ola Undrum; Søraas, Camilla Lund; Larstorp, Anne Cecilie Kjeldsen; Hjørnholm, Ulla & Kjær, Vibeke Norheim [Vis alle 14 forfattere av denne artikkelen] (2022). Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy. Journal of the American Heart Association (JAHA). ISSN 2047-9980. 11(18). doi: 10.1161/JAHA.121.025879. Fulltekst i vitenarkiv Vis sammendrag

  Background Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment‐resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy. Methods and Results Nineteen patients assumed to have true treatment‐resistant hypertension and adherence to antihypertensive drugs based on directly observed therapy were investigated repeatedly through 7 years. Serum concentrations of antihypertensive drugs were measured by ultra‐high‐performance liquid chromatography–tandem mass spectrometry from blood samples taken at baseline, 6‐month, 3‐year, and 7‐year visits. Cytochrome P450 polymorphisms, self‐reported adherence and beliefs about medicine were performed as supplement investigations. Seven patients (37%) were redefined as nonadherent based on their serum concentrations during follow‐up. All patients reported high adherence to medications. Nonadherent patients expressed lower necessity and higher concerns regarding intake of antihypertensive medication (P=0.003). Cytochrome P450 polymorphisms affecting metabolism of antihypertensive drugs were found in 16 patients (84%), 21% were poor metabolizers, and none were ultra‐rapid metabolizers. Six of 7 patients redefined as nonadherent had cytochrome P450 polymorphisms, however, not explaining the low serum drug concentrations measured in these patients. Conclusions Our data suggest that repeated measurements of serum concentrations of antihypertensive drugs revealed nonadherence in one‐third of patients previously evaluated as adherent and treatment resistant by directly observed therapy, thereby improving the accuracy of adherence evaluation. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT01673516.

• Thorstensen, Christian; Clasen, Per-Erik; Rognstad, Stine; Haldsrud, Renate; Føreid, Siri & Helstrøm, Trine [Vis alle 16 forfattere av denne artikkelen] (2022). Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 219. doi: 10.1016/j.jpba.2022.114908. Fulltekst i vitenarkiv Vis sammendrag

  We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLC-MS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs. For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for all drugs was 4–28 %. The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the recommended maximum daily dose. We report the maximum (Cmax) and minimum (Cmin) drug concentrations after drug intake. The inter-individual pharmacokinetic variability at Cmin was 18-fold for hydrochlorothiazide, 22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan. Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control.

• Bergland, Ola Undrum; Halvorsen, Lene Vernås; Søraas, Camilla Lund; Hjørnholm, Ulla; Kjær, Vibeke Norheim & Rognstad, Stine [Vis alle 22 forfattere av denne artikkelen] (2021). Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations. Hypertension. ISSN 0194-911X. 78(3), s. 617–628. doi: 10.1161/HYPERTENSIONAHA.121.17514. Fulltekst i vitenarkiv Vis sammendrag

  Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.

• Rognstad, Stine; Søraas, Camilla Lund; Bergland, Ola Undrum; Høieggen, Aud; Strømmen, Magnus & Helland, Arne [Vis alle 7 forfattere av denne artikkelen] (2020). Establishing Serum Reference Ranges for Antihypertensive Drugs. Therapeutic Drug Monitoring. ISSN 0163-4356. 43(1), s. 116–125. doi: 10.1097/FTD.0000000000000806. Fulltekst i vitenarkiv
• Burns, Margrete Larsen; Kinge, Einar; Opdal, Mimi Stokke; Johannessen, Svein Ivar & Landmark, Cecilie Johannessen (2019). Therapeutic drug monitoring of gabapentin in various indications. Acta Neurologica Scandinavica. ISSN 0001-6314. 139(5), s. 446–454. doi: 10.1111/ane.13075.
• Muller, Lill Dannevig & Opdal, Mimi Stokke (2018). Developing a rapid semi-automated sample preparation with alkaline hydrolysis in a 96-well plate for quantification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine samples by UHPLC-MS/MS. Journal of Pharmaceutical and Biomedical Analysis. ISSN 0731-7085. 161, s. 296–304. doi: 10.1016/j.jpba.2018.08.045.
• Haga, Christian; Opdal, Mimi Stokke; Tuv, Silja Skogstad; Zahl, Per Henrik & Stenberg-Nilsen, Hanne (2016). Legemiddelsikkerhet ved bytte av digitalispreparat i Norge. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 136(20), s. 1714–1718. doi: 10.4045/tidsskr.15.0161.
• Burns, Margrete Larsen; Baftiu, Arton; Opdal, Mimi Stokke; Johannessen, Svein Ivar & Landmark, Cecilie Johannessen (2016). Therapeutic drug monitoring of clobazam and its metabolite-impact of age and comedication on pharmacokinetic variability. Therapeutic Drug Monitoring. ISSN 0163-4356. 38(3), s. 350–357. doi: 10.1097/FTD.0000000000000272.
• Opdal, Mimi Stokke; Arnesen, Margrete; Muller, Lill Dannevig; Hullstein, Ingunn; Sayed, Karim & Brørs, Odd [Vis alle 10 forfattere av denne artikkelen] (2015). Effects of Hemodialysis on Methadone Pharmacokinetics and QTc. Clinical Therapeutics. ISSN 0149-2918. 37(7), s. 1594–1599. doi: 10.1016/j.clinthera.2015.04.009.
• Kristiansen, Marianne; Piehler, Armin; Grimholt, Runa Marie; Opdal, Mimi Stokke; Foss, Kari Bente & Urdal, Petter (2014). Serum bilirubin concentration in healthy adult North-Europeans is strictly controlled by the UGT1A1 TARepeat variants. PLOS ONE. ISSN 1932-6203. 9(2). doi: 10.1371/journal.pone.0090248.
• Kristiansen, Marianne; Foss, Kari Bente; Grimholt, Runa Marie; Stormo, Camilla; Narum, Sigrid & Opdal, Mimi S. [Vis alle 12 forfattere av denne artikkelen] (2011). Genetic Variation of VKORC1 and CYP4F2 Genes Related to Warfarin Maintenance Dose in Patients with Myocardial Infarction. Journal of Biomedicine and Biotechnology. ISSN 1110-7243. 2011. doi: 10.1155/2011/739751.
• Al-Samarraie, MSJ; Karinen, Ritva Anneli; Mørland, Jørg & Opdal, Mimi Stokke (2010). Blood GHB concentrations and results of medical examinations in 25 car drivers in Norway. European Journal of Clinical Pharmacology. ISSN 0031-6970. 66(10), s. 987–998. doi: 10.1007/s00228-010-0870-x.
• Øiestad, Elisabeth Leere; Johansen, Unni; Mimi Stokke, Opdal; Bergan, Stein & Christophersen, Asbjørg S. (2009). Determination of digoxin and digitoxin in whole blood. Journal of Analytical Toxicology. ISSN 0146-4760. 33(7), s. 372–378.
• Samarrai, Al; Karinen, Ritva Anneli; Rognum, T; Hasvold, Inger; Mimi Stokke, Opdal & Christophersen, Asbjørg S. (2009). Lethal Poisoning with Ethiofencarb and Ethanol. Journal of Analytical Toxicology. ISSN 0146-4760. 33(7), s. 389–392.
• Khiabani, Hassan; Mimi Stokke, Opdal & Mørland, Jørg (2008). Blood alcohol concentrations in apprehended drivers of cars and boats suspected to be impaired by the police. Traffic Injury Prevention. ISSN 1538-9588. 9(1), s. 31–36. doi: 10.1080/15389580701737629.
• Al-Samarraie, Muhammad; Khiabani, Hassan & Opdal Stokke, Mimi (2007). Khat - et nytt rusmiddel i Norge. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 127(5), s. 574–576.
• Bernard, Jean-Paul; Opdal Stokke, Mimi; Karinen, Ritva Anneli; Mørland, Jørg & Khiabani, Hassan (2007). Relationship between methadone and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) in urine samples from Norwegian prisons. European Journal of Clinical Pharmacology. ISSN 0031-6970. 63(8), s. 777–782. doi: 10.1007/s00228-007-0314-4. Vis sammendrag

  Background: Methadone is a widely used maintenance treatment in rehabilitation of opioid addiction the world over. Methadone is metabolised in the body to a number of inactive metabolites, but primarily to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). The Division of Forensic Toxicology and Drug Abuse (DFTDA), at the Norwegian Institute of Public Health, carries out drug analysis in urine samples from all prisons in Norway. Testing for methadone and EDDP in urine is also carried out, on request. Results are stored in a secure database at the DFTDA. Objectives: The aims of the present study were to 1. Observe variation of methadone and EDDP concentrations in urine with urinary pH, in a large material of prison inmate urine samples, and 2. Analyse methadone positive/EDDP negative results, and investigate whether such results could occur naturally and without sample tampering. Methods: All urine results positive for methadone over the period 2004-2005 were collected from our result database. The relationship between methadone and EDDP excretion in urine, and urinary pH, was observed for these cases. Cases that were positive for methadone but negative for EDDP were picked out and studied individually. Results: 1539 urine samples positive for methadone were found in our database for the period 2004-2005. Our results showed a strong correlation between the concentration of methadone in urine and urinary pH, with higher concentrations of methadone present at lower pH levels. Cases that were positive for methadone but negative for EDDP were rare, and amounted to only 5 (0.3% of the case material). These cases are presented in further detail. Conclusion: Methadone excretion in urine is dependent on urinary pH. Methadone positive/EDDP negative results may suggest sample tampering in some, but not all, cases.

• Kristoffersen, Lena; Øiestad, Elisabeth Leere; Opdal , Mimi Stokke; Krogh, Mette; Lundanes, Elsa & Christophersen, Asbjørg S. (2007). Simultaneous determination of 6 beta-blockers, 3 calcium-channel antagonists, 4 angiotensin-II antagonists and 1 antiarrhytmic drug in post-mortem whole blood by automated solid phase extraction and liquid chromatography mass spectrometry - Method development and robustness testing by experimental design. Journal of chromatography. B. ISSN 1570-0232. 850(1-2), s. 147–160. doi: 10.1016/j.jchromb.2006.11.030.
• Stokke, Mimi; Grønvold, Trude; Siebke, Anne Marie; Skjæggestad, O & Strømme, Johan Henrik (1998). Serial measurements of cardiac markers to rule in or out acute myocardial damage less than 3 h after admission in acute chest pain patients without ECG-signs of acute myocardial infarction. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 58(4), s. 331–338.
• Stokke, Mimi; Kirkebøen, Knut Arvid; Næss, Pål Aksel; Hagelin, Else Marie; Ilebekk, Arnfinn & Brørs, Odd (1996). Equal changes in L-type calcium channel density after 60 min of ischaemia in normal and ischaemically preconditioned porcine myocardium. Acta Physiologica Scandinavica. ISSN 0001-6772. 157(2), s. 147–155.
• Stokke, Mimi; Hagelin, Else Marie & Brørs, Odd (1996). Effects of ATP on specific [3H](+)-isradipine binding in rat ventricular cardiomyocytes. European Journal of Pharmacology. ISSN 0014-2999. 303(1-2), s. 115–122.
• Stokke, Mimi; Hagelin, Else Marie; Mende, Ulrike & Brørs, Odd (1996). Stable guanosine 5'-triphosphate-analogues inhibit specific (+)-[3H]isradipine binding in rat hearts by a Ca(2+)-lowering, G protein-independent mechanism. Pharmacology and Toxicology. ISSN 0901-9928. 78(1), s. 28–36.
• Stokke, Mimi; Aksnes, Gunnar; Lande, Knut; Hagelin, Else Marie & Brørs, Odd (1994). Density of L-type calcium channels in ischaemically preconditioned porcine heart regions. Acta Physiologica Scandinavica. ISSN 0001-6772. 150(4), s. 425–430.
• Stokke, Mimi; Hagelin, Else Marie; Poulsson, Claire & Brørs, Odd (1992). Ca2+ modulates the inhibition of (+)-[3H]isradipine binding by amiloride and quinacrine. European Journal of Pharmacology. ISSN 0014-2999. 227(4), s. 379–384.
• Stokke, Mimi; Hagelin, Else Marie; Poulsson, Claire; Patel, Renuka; Haile, Y & Brørs, Odd (1992). Inhibition by amiloride and quinacrine of specific [3H]nitrendipine binding to rat cardiac membranes. Journal of Pharmacology and Experimental Therapeutics. ISSN 0022-3565. 260(3), s. 1366–1372.

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• Halvorsen, Lene Vernås; Gognstad, Stine; Søraas, Camilla Lund; Ågnes, Camilla; Hjørnholm, Ulla & Kjær, Vibeke Norheim [Vis alle 21 forfattere av denne artikkelen] (2022). Implications of CYP2D6 polymorphisms for therapeutic drug monitoring in patients with hypertension. Journal of Hypertension. ISSN 0263-6352. 40. doi: 10.1097/01.hjh.0000838764.61491.a8.
• Opdal, Mimi Stokke & Krajci, Peter (2017). Individual dosing of a methadone maintenance patient with reported opioid withdrawal symptoms.
• Opdal, Mimi Stokke & Johansen, Per Wiik (2016). Nyttig og nødvendig om nye antikoagulasjonsmidler. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 136(18), s. 1505–1505. doi: 10.4045/tidsskr.16.0786.
• Mimi Stokke, Opdal (2007). A report of findings of some cardiovascular drugs in postmortem whole blood.
• Bernard, Jean-Paul; Opdal Stokke, Mimi; Mørland, Jørg & Khiabani, Hassan Zare (2007). Methadone related deaths in Norway 2004 - 2006. Vis sammendrag

  Objective: Methadone, a potent opioid receptor agonist, is the most commonly used drug in the treatment of opioid dependence in Norway. Methadone’s side-effects and toxicity are well documented, and the potential for a rise in the incidence of methadone related deaths due to greater methadone availability is worrying. This study aims to follow the occurrence and pattern of methadone related deaths over a three year period. We will also examine cases where methadone was present at toxicological analysis post-mortem and assess what role methadone toxicity played in the cause of death. Methods: Toxicological results where methadone was positive were collected from a database of forensic autopsies at the Division of Forensic Toxicology and Drug Abuse (DFTDA). Cases were divided into those where methadone was the only drug present and those where other drugs were present in addition to methadone. All cases were assessed individually. Results: A total of 176 methadone related deaths were identified from our database of approximately 5400 cases for the period 2004 through 2006. Of these, 143 were male and 33 female. Methadone was the only finding at toxicological analysis in just 6 (3.4%) of these cases. Methadone concentrations in blood varied from 0.06 mg/l to 4.64 mg/l, with a median concentration of 0.43 mg/l. A variety of other substances were also detected in blood, the 3 most common being tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis), and metabolic products of the benzodiazepines diazepam (N-desmethyldiazepam) and clonazepam (7-aminoclonazepam), respectively. Morphine was detected in 35 cases. The mean number of additional substances detected in these cases was 4. Conclusion: Methadone related deaths in Norway have risen over the past years. Methadone was most often detected in combination with other substances. These results may suggest that patients using methadone have a significant use of other substances, both illegal and prescription medicines. Alternatively, results may indicate that the majority of those involved in methadone related deaths are not enrolled in rehabilitation programs, and that the source of methadone in these cases is diversion. The study is still ongoing, and further analysis of the results is necessary. We are in the process of coupling our material to the National cause of death register and regional registers of patients enrolled in rehabilitation programs (LAR).

• Bernard, Jean-Paul; Opdal Stokke, Mimi & Khiabani, Hassan (2006). Generelle farmakodynamiske prinsipper. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 126(16), s. 2107–2109. Vis sammendrag

  Sammendrag: Farmakodynamikk handler om hvordan ligander (legemidler, rusmidler, giftstoffer og hormoner) virker på sine målorganer i kroppen og utløser effekter (enten ønsket eller uønsket). Interaksjon mellom legemidler og mottakerproteiner er spesifikk og selektiv i organismen. Mottakerproteinene tilhører stort sett til en av fire grupper; enzymer, transportproteiner, ionekanaler og reseptorer.

• Mimi Stokke, Opdal (2006). Dextropropoxyphene concentrations in blood sampled from forensic autopsies.
• Opdal, Mimi Stokke (2004). Clinical pharmacology Education and Inturnship. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 124(13-14), s. 1828–1829.
• Opdal, Mimi Stokke (1996). Modulation of cardiac Ca2+ antagonist binding by drugs, nucleotides, divalent cations and ischemia. Department of Pharmacology, Faculty of Medicine, University of Oslo and Division of Clinical Pharmacology and Toxicology, Clinical Chemistry Department, Ullevål University Hospital [Norwegian Society. ISSN 0802-1465. 9(Suppl.5).

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