{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:25:33Z","timestamp":1790126733168,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T00:00:00Z","timestamp":1520553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Intravenous high\u2010dose free methylprednisolone (MP) hemisuccinate is the primary treatment for an acute relapse in relapsing\u2013remitting multiple sclerosis. However, it is inconvenient and its side effects are undesirable. Both dose and dosing frequency can be reduced by incorporating free MP in glutathione\u2010PEGylated liposomes, creating a slow\u2010release formulation with reduced toxicity and prolonged peripheral efficacy. This first\u2010in\u2010human study was designed to assess the safety, pharmacokinetics and pharmacodynamics of glutathione\u2010PEGylated liposomes containing MP (2B3\u2013201).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The first part was a double\u2010blind, three\u2010way cross over study in 18 healthy male subjects, receiving ascending doses of 2B3\u2013201, active comparator (free MP) or placebo. Part 2 of the study was an open\u2010label infusion of 2B3\u2013201 (different doses), exploring pretreatment with antihistamines and different infusion schedules in another 18 healthy male subjects, and a cross\u2010over study in six healthy female subjects. MP plasma concentrations, lymphocyte counts, adrenocorticotropic hormone, osteocalcin and fasting glucose were determined. Safety and tolerability profiles were assessed based on adverse events, safety measurements and central nervous system tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The most frequent recorded AE related to 2B3\u2013201 was an infusion related reaction (89%). 2B3\u2013201 was shown to have a plasma half\u2010life between 24 and 37\u00a0h and caused a prolonged decrease in the lymphocyte count, adrenocorticotropic hormone and osteocalcin, and a rise in fasting glucose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>2B3\u2013201 is considered safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events. In addition, 2B3\u2013201 shows a long plasma half\u2010life and prolonged immunosuppressive effects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13525","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T22:36:04Z","timestamp":1517438164000},"page":"1020-1028","source":"Crossref","is-referenced-by-count":31,"title":["Glutathione\u2010PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first\u2010in\u2010human study"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-6467","authenticated-orcid":false,"given":"K. M. S.","family":"Kanhai","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. G. J. 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