Phase 1 Dose‐Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Tofacitinib in Japanese Healthy Volunteers
| العنوان: | Phase 1 Dose‐Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Tofacitinib in Japanese Healthy Volunteers |
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| المؤلفون: | So Miyoshi, Samuel H. Zwillich, Shigeyuki Toyoizumi, Sriram Krishnaswami, Hiroyuki Nakamura |
| المصدر: | Clinical Pharmacology in Drug Development |
| بيانات النشر: | John Wiley and Sons Inc., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Genotype, Pharmaceutical Science, Original Manuscript, Placebo, 030226 pharmacology & pharmacy, Gastroenterology, White People, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Asian People, Double-Blind Method, Piperidines, Internal medicine, medicine, Humans, Pharmacology (medical), Adverse effect, Protein Kinase Inhibitors, Janus kinase inhibitor, Tofacitinib, tofacitinib, business.industry, Articles, Middle Aged, medicine.disease, Ulcerative colitis, Healthy Volunteers, Cytochrome P-450 CYP2C19, Pyrimidines, Tolerability, phase 1, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Japanese, Female, business, pharmacokinetics, Western |
| الوصف: | The aim of the study was to characterize the pharmacokinetics, safety, and tolerability of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis in healthy Japanese volunteers, and to compare these outcomes with those of healthy Western volunteers. Twenty‐five volunteers (Japanese, n = 16; Western [white], n = 9) were randomized to receive either 3 escalating single doses of tofacitinib (1, 5, and 30 mg), single‐dose tofacitinib (15 mg) followed by multiple doses (15 mg twice daily for 5 days), or placebo. No significant differences in systemic exposure to tofacitinib were detected between the 2 ethnicities. Following single tofacitinib 1, 5, and 30 mg doses, mean area under the plasma concentration–time curve from time zero to infinity ratio (Japanese/Western) values were 96.6%, 93.5%, and 95.6%, respectively. Similarly, mean maximum observed plasma concentration ratio values were 99.5%, 118%, and 119%, respectively. Mean renal clearance was also similar, ranging across doses from 134 mL/min (5 mg) to 162 mL/min (1 mg) in Japanese volunteers, and 124 mL/min (30 mg) to 160 mL/min (1 mg) in Western volunteers. In both ethnicities, most adverse events were mild. No serious adverse events or deaths were reported. The pharmacokinetics of tofacitinib were well characterized in healthy Japanese volunteers and were similar to those in Western volunteers. |
| اللغة: | English |
| تدمد: | 2160-7648 2160-763X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f58b61815e97914a213125c1ea8a859aTest http://europepmc.org/articles/PMC7003739Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f58b61815e97914a213125c1ea8a859a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21607648 2160763X |
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