Academic Journal
Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects
| العنوان: | Single Ascending Dose Study to Assess Pharmacokinetic Linearity, Safety, and Tolerability of Trimetazidine - Modified Release in Healthy Human Subjects |
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| المؤلفون: | Körnicke, Thomas, Arora, Deepa, Samad, Abdus, Kaplan, Sigal, Domahidy, Mónika, de Voogd, Hanka, Böhmert, Stella, Ramos, Rita Silveira, Jain, Shashank |
| المصدر: | Drug Research ; volume 70, issue 10, page 472-477 ; ISSN 2194-9379 2194-9387 |
| بيانات النشر: | Georg Thieme Verlag KG |
| سنة النشر: | 2020 |
| الوصف: | Aim This study assessed the linearity of pharmacokinetics (PK) of trimetazidine (TMZ) modified-release tablets (indicated in adults as an add-on therapy for stable angina pectoris) and measured its renal elimination, safety, and tolerability in healthy subjects. Methods This was a randomized, open-label, single-ascending dose study in healthy subjects. Subjects were administered with a single dose of 35, 70, or 105 mg TMZ-modified release tablets (six subjects each). Pharmacokinetic evaluations and safety analysis were performed before the first dose and till 48 h post-first dose. Results Following administration of 35, 70, and 105 mg TMZ-modified release; the Cmax (mean±SD) was 79.32 (±23.08), 153.17 (±23.08), and 199.67 (±23.08) ng/mL, the Tmax was 5.42 (±0.49), 4.51 (±1.27), and 4.57 (±0.96) h, t1/2 was 7.75 (±1.62), 6.40 (±1.23), and 6.50 (±1.18) h, AUC(0-inf) was 1116.89 (±378.35), 1838.39 (±284.50), and 2504.84 (±348.35) ng.h/mL, CLR was 13.70 (±2.24), 14.80 (±5.91), and 19.58 (±6.24) L·h−1 and CL/F was 33.69 (±8.51), 38.85 (±6.15), and 42.74 (±7.10) L·h−1, respectively. Slope estimates for AUC(0-inf), AUC(0-t), and Cmax were less than 1. Corresponding 95% CI of the slope for the AUC parameters excluded 1, indicating that the deviation from dose-proportionality was statistically significant. Corresponding 95% CI of the slope for Cmax included 1, indicating that the less than dose-proportional increase in Cmax was not statistically significant. No significant adverse events were observed. Conclusion Substantial deviation from a dose-proportional increase in AUC(0-inf) and AUC(0-t) suggested a non-linear PK for TMZ-modified release. Single dose of TMZ-modified release was well tolerated and safe. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1055/a-1180-4357 |
| DOI: | 10.1055/a-1180-4357.pdf |
| الاتاحة: | http://dx.doi.org/10.1055/a-1180-4357 http://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-1180-4357.pdf |
| رقم الانضمام: | edsbas.C019CB0D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1055/a-1180-4357 |
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