Henrik Uebel-von Sandersleben, Anke Mayer, Michaela Ruhmann, Oliver Dangel, Helmut Schütz
{"title":"健康成人单次和多次给药后缓释硫酸右安非他明制剂的药代动力学:与速释硫酸右安非他明的比较生物利用度、强度、食品和膳食成分效应评估","authors":"Henrik Uebel-von Sandersleben, Anke Mayer, Michaela Ruhmann, Oliver Dangel, Helmut Schütz","doi":"10.2478/sjcapp-2023-0014","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>A modified-release dexamphetamine sulfate formulation (DEX-MR) is under development for the treatment of attention-deficit/hyperactivity disorder.</p><p><strong>Objective: </strong>We investigated the bioequivalence of once-daily DEX-MR to twice-daily immediate-release dexamphetamine sulfate (DEX-IR) after single and multiple dosing and between strengths, and effects of food and meal types.</p><p><strong>Method: </strong>Three randomized, open-label, crossover studies in healthy males were conducted. In the single-dose study, participants received DEX-MR 20 mg, DEX-MR 10 mg (20 mg dose), and twice-daily DEX-IR 10 mg under fasted conditions and after a high-fat, high-calorie breakfast. In the breakfast study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg after a normocaloric and a high-fat, high-calorie breakfast. In the multiple-dose study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg for seven days each. In the run-in period (five days), participants consumed a normocaloric breakfast; on profile days, participants consumed a normocaloric breakfast (day 6) or a high-fat, high-calorie breakfast (day 7).</p><p><strong>Results: </strong>Once-daily DEX-MR at a dose of 20 mg was bioequivalent to twice-daily DEX-IR 10 mg after single dosing under fasted and fed conditions and after multiple dosing under fed conditions. DEX-MR 10 mg and DEX-MR 20 mg were bioequivalent when administered as a single 20 mg dose. Food slightly reduced the rate and extent of absorption of DEX-MR and delayed the time to peak plasma concentration (<i>t</i><sub>max</sub>) by approximately two hours compared to the fasted state. Bioavailability of DEX-MR was comparable under different meal conditions (normocaloric vs. high-fat, high-calorie breakfast) both after single and multiple dosing.</p><p><strong>Conclusions: </strong>Bioequivalence of once-daily DEX-MR and twice-daily DEX-IR was established. 1×2 DEX-MR 10 mg was bioequivalent to 1×1 DEX-MR 20 mg. DEX-MR should be administered with/after a meal to achieve the targeted pharmacokinetic profile (delayed <i>t</i><sub>max</sub>). Bioavailability of DEX-MR is not affected by meal composition (i.e., fat and caloric content).</p>","PeriodicalId":42655,"journal":{"name":"Scandinavian Journal of Child and Adolescent Psychiatry and Psychology","volume":"11 1","pages":"132-142"},"PeriodicalIF":1.4000,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687392/pdf/","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetics of a Modified-Release Dexamphetamine Sulfate Formulation Following Single and Multiple Dosing in Healthy Adults: Comparative Bioavailability with Immediate-Release Dexamphetamine Sulfate, between Strengths, Assessment of Food and Meal Composition Effects.\",\"authors\":\"Henrik Uebel-von Sandersleben, Anke Mayer, Michaela Ruhmann, Oliver Dangel, Helmut Schütz\",\"doi\":\"10.2478/sjcapp-2023-0014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>A modified-release dexamphetamine sulfate formulation (DEX-MR) is under development for the treatment of attention-deficit/hyperactivity disorder.</p><p><strong>Objective: </strong>We investigated the bioequivalence of once-daily DEX-MR to twice-daily immediate-release dexamphetamine sulfate (DEX-IR) after single and multiple dosing and between strengths, and effects of food and meal types.</p><p><strong>Method: </strong>Three randomized, open-label, crossover studies in healthy males were conducted. In the single-dose study, participants received DEX-MR 20 mg, DEX-MR 10 mg (20 mg dose), and twice-daily DEX-IR 10 mg under fasted conditions and after a high-fat, high-calorie breakfast. In the breakfast study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg after a normocaloric and a high-fat, high-calorie breakfast. In the multiple-dose study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg for seven days each. In the run-in period (five days), participants consumed a normocaloric breakfast; on profile days, participants consumed a normocaloric breakfast (day 6) or a high-fat, high-calorie breakfast (day 7).</p><p><strong>Results: </strong>Once-daily DEX-MR at a dose of 20 mg was bioequivalent to twice-daily DEX-IR 10 mg after single dosing under fasted and fed conditions and after multiple dosing under fed conditions. DEX-MR 10 mg and DEX-MR 20 mg were bioequivalent when administered as a single 20 mg dose. Food slightly reduced the rate and extent of absorption of DEX-MR and delayed the time to peak plasma concentration (<i>t</i><sub>max</sub>) by approximately two hours compared to the fasted state. Bioavailability of DEX-MR was comparable under different meal conditions (normocaloric vs. high-fat, high-calorie breakfast) both after single and multiple dosing.</p><p><strong>Conclusions: </strong>Bioequivalence of once-daily DEX-MR and twice-daily DEX-IR was established. 1×2 DEX-MR 10 mg was bioequivalent to 1×1 DEX-MR 20 mg. DEX-MR should be administered with/after a meal to achieve the targeted pharmacokinetic profile (delayed <i>t</i><sub>max</sub>). Bioavailability of DEX-MR is not affected by meal composition (i.e., fat and caloric content).</p>\",\"PeriodicalId\":42655,\"journal\":{\"name\":\"Scandinavian Journal of Child and Adolescent Psychiatry and Psychology\",\"volume\":\"11 1\",\"pages\":\"132-142\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2023-11-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687392/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scandinavian Journal of Child and Adolescent Psychiatry and Psychology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2478/sjcapp-2023-0014\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scandinavian Journal of Child and Adolescent Psychiatry and Psychology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2478/sjcapp-2023-0014","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Pharmacokinetics of a Modified-Release Dexamphetamine Sulfate Formulation Following Single and Multiple Dosing in Healthy Adults: Comparative Bioavailability with Immediate-Release Dexamphetamine Sulfate, between Strengths, Assessment of Food and Meal Composition Effects.
Background: A modified-release dexamphetamine sulfate formulation (DEX-MR) is under development for the treatment of attention-deficit/hyperactivity disorder.
Objective: We investigated the bioequivalence of once-daily DEX-MR to twice-daily immediate-release dexamphetamine sulfate (DEX-IR) after single and multiple dosing and between strengths, and effects of food and meal types.
Method: Three randomized, open-label, crossover studies in healthy males were conducted. In the single-dose study, participants received DEX-MR 20 mg, DEX-MR 10 mg (20 mg dose), and twice-daily DEX-IR 10 mg under fasted conditions and after a high-fat, high-calorie breakfast. In the breakfast study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg after a normocaloric and a high-fat, high-calorie breakfast. In the multiple-dose study, participants received DEX-MR 20 mg and twice-daily DEX-IR 10 mg for seven days each. In the run-in period (five days), participants consumed a normocaloric breakfast; on profile days, participants consumed a normocaloric breakfast (day 6) or a high-fat, high-calorie breakfast (day 7).
Results: Once-daily DEX-MR at a dose of 20 mg was bioequivalent to twice-daily DEX-IR 10 mg after single dosing under fasted and fed conditions and after multiple dosing under fed conditions. DEX-MR 10 mg and DEX-MR 20 mg were bioequivalent when administered as a single 20 mg dose. Food slightly reduced the rate and extent of absorption of DEX-MR and delayed the time to peak plasma concentration (tmax) by approximately two hours compared to the fasted state. Bioavailability of DEX-MR was comparable under different meal conditions (normocaloric vs. high-fat, high-calorie breakfast) both after single and multiple dosing.
Conclusions: Bioequivalence of once-daily DEX-MR and twice-daily DEX-IR was established. 1×2 DEX-MR 10 mg was bioequivalent to 1×1 DEX-MR 20 mg. DEX-MR should be administered with/after a meal to achieve the targeted pharmacokinetic profile (delayed tmax). Bioavailability of DEX-MR is not affected by meal composition (i.e., fat and caloric content).