Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder
| العنوان: | Pharmacokinetics of Sublingual Buprenorphine Tablets Following Single and Multiple Doses in Chinese Participants With and Without Opioid Use Disorder |
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| المؤلفون: | Dandan Li, Liwei Lang, Frank Gray, Hongyun Wang, Malcolm A. Young, Ji Jiang, Zeyuan Liu, Céline M. Laffont, Ruihua Dong, Susan M Learned, Yongzhen Liu |
| المصدر: | Drugs in R&D Drugs in R&D, Vol 19, Iss 3, Pp 255-265 (2019) |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Male, Administration, Sublingual, Cmax, Biological Availability, 030226 pharmacology & pharmacy, Naltrexone, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Asian People, Naloxone, medicine, Humans, Original Research Article, Norbuprenorphine, 030203 arthritis & rheumatology, Pharmacology, business.industry, lcsh:RM1-950, Area under the curve, Opioid use disorder, Opioid-Related Disorders, medicine.disease, Buprenorphine, Analgesics, Opioid, lcsh:Therapeutics. Pharmacology, chemistry, Opioid, Area Under Curve, Anesthesia, Female, business, Tablets, medicine.drug |
| الوصف: | Background Two phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants. Methods In the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block. In a second phase I, open-label, multiple ascending-dose (MAD) study, 27 patients with opioid dependence in withdrawal received buprenorphine/naloxone doses of either 16 mg/4 mg or 24 mg/6 mg for 9 consecutive days. Serial blood samples were collected after a single dose (SAD study) and at steady-state (MAD study). Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety assessments included adverse events monitoring and laboratory tests. Results The pharmacokinetic profiles of buprenorphine and naloxone were consistent between single- and multiple-dose studies. Peak plasma concentrations (Cmax) were reached early for buprenorphine (0.75–1.0 h) and naloxone (0.5 h), supporting rapid absorption. In the SAD study, increases in plasma exposures to buprenorphine and naloxone were less than dose proportional, in line with previous observations in Western populations. Buprenorphine-to-naloxone ratios for Cmax and area under the curve (AUC) were constant over the dose range investigated and also consistent with Western populations data. Steady state was reached within 7 days of daily dosing, with slight accumulation over repeated doses. No serious adverse events were observed. Conclusions The present data suggest that buprenorphine/naloxone pharmacokinetic profiles in Chinese participants are consistent, overall, with those in Western populations, supporting no differences in dosing. Clinical Trial Registration The protocols were registered on the official website of the China Food and Drug Administration (CFDA): http://www.chinadrugtrials.org.cn/; Registration numbers CTR20132963 (RB-CN-10-0012), CTR20140153 (RB-CN-10-0015). Electronic supplementary material The online version of this article (10.1007/s40268-019-0277-9) contains supplementary material, which is available to authorized users. |
| تدمد: | 1179-6901 1174-5886 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c8ab17c278e417c8cd6e813ec459e8c https://doi.org/10.1007/s40268-019-0277-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3c8ab17c278e417c8cd6e813ec459e8c |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 11796901 11745886 |
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