{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T11:41:07Z","timestamp":1776944467552,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bacterial infection of the intervertebral disc is difficult to treat because the tissue is usually not vascularized and systemic antibiotic therapy may not reach optimal antibacterial exposure. Here we characterize the safety, tolerability, and pharmacokinetics of PP353, a suspension of micronized linezolid, formulated for direct intervertebral disc administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The safety, tolerability, and pharmacokinetics of an intradiscal administration of PP353, was assessed in Part A of a Phase 1b study and consisted of a single injection of study drug (3\u2009mL of PP353 and 150\u2009mg linezolid). Clinical assessment included initial safety and tolerability of PP353 with continued follow\u2010up for 12\u2009months. Assessment of linezolid concentration in plasma samples enabled characterization of the pharmacokinetics. Deconvolution of systemic linezolid was used to estimate intervertebral disc linezolid concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intradiscal administration of 3\u2009mL of PP353 (linezolid 50\u2009mg\/mL) to the nucleus pulposus was well tolerated with no reported study treatment\u2010related severe or serious adverse events and resulted in an average geometric mean linezolid plasma <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> of 1300\u2009ng\/mL at 7.27\u2009h post\u2010administration. The linezolid plasma <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> observed with intradiscal PP353 is approximately 10% that observed with a standard oral or iv administration of 600\u2009mg linezolid. Pharmacokinetic deconvolution estimated that a single dose of PP353 (150\u2009mg linezolid) provided intradiscal bactericidal concentration of linezolid for 96\u2009h and bacteriostatic exposure for up to 120\u2009h after dosing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intradiscal administration of 3\u2009mL of PP353 is well\u2010tolerated and based on the pharmacokinetics following a single injection, a two\u2010dose regimen of PP353 (150\u2009mg linezolid) on Day 1 and Day 5\u2009\u00b1\u20091 was selected to explore safety, tolerability, pharmacokinetics, and efficacy in Part B of the Persica 002 study.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsp2.70009","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T11:56:01Z","timestamp":1731585361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of <scp>PP353<\/scp>, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first\u2010in\u2010human, Phase 1b, open\u2010label, single\u2010dose study"],"prefix":"10.1002","volume":"7","author":[{"given":"Shiva S.","family":"Tripathi","sequence":"first","affiliation":[{"name":"NIHR Lancashire Clinical Research Facility, Lancashire Teaching Hospitals NHS Foundation Trust  Preston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sneath","sequence":"additional","affiliation":[{"name":"NIHR Coventry and Warwickshire Clinical Research Facility University Hospitals Coventry and Warwickshire NHS Trust  Coventry UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aprajay","family":"Golash","sequence":"additional","affiliation":[{"name":"NIHR Lancashire Clinical Research Facility, Lancashire Teaching Hospitals NHS Foundation Trust  Preston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parag","family":"Desai","sequence":"additional","affiliation":[{"name":"NIHR Lancashire Clinical Research Facility, Lancashire Teaching Hospitals NHS Foundation Trust  Preston UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"McHale","sequence":"additional","affiliation":[{"name":"Weatherden Ltd  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Guest","sequence":"additional","affiliation":[{"name":"Persica Pharmaceuticals Ltd  Canterbury Kent UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlie","family":"Brindley","sequence":"additional","affiliation":[{"name":"Kinetassist Ltd  Quothquan UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Cummings","sequence":"additional","affiliation":[{"name":"PJC Pharma Consulting Ltd  Suffolk UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shane","family":"Smith","sequence":"additional","affiliation":[{"name":"PJC Pharma Consulting Ltd  Suffolk UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conrad","family":"Stroud","sequence":"additional","affiliation":[{"name":"Micron Research Ltd  Ely UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Scott","sequence":"additional","affiliation":[{"name":"GS Drug Development Sciences Ltd  East Grinsted UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Ruston","sequence":"additional","affiliation":[{"name":"Persica Pharmaceuticals Ltd  Canterbury Kent UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8263-0190","authenticated-orcid":false,"given":"Lloyd","family":"Czaplewski","sequence":"additional","affiliation":[{"name":"Persica Pharmaceuticals Ltd  Canterbury Kent UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44259\u2010023\u201000002\u20107"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy037"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0875"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296\u2010016\u20103532\u20101"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.11.011"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bas.2023.101733"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010013\u20102674\u2010z"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010016\u20104887\u20104"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174518"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161676"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(00)05109\u20106"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0b013e318269851a"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0b013e3182019f3a"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010015\u20104180\u2010y"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001909"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/6192935"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891\u2010018\u20102373\u20103"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.7910"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010013\u20102675\u2010y"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l5654"},{"key":"e_1_2_13_22_1","doi-asserted-by":"crossref","unstructured":"HaggerG GuestS BirchallS et al.Preclinical Development and Characterisation of PP353 A Formulation of Linezolid for Intradiscal Administration.2024. doi:10.1002\/jsp2.70010","DOI":"10.1002\/jsp2.70010"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.4184\/asj.2017.11.3.380"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000267518.20363.0d"},{"key":"e_1_2_13_25_1","first-page":"115","article-title":"Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose","volume":"9","author":"Miller MR","year":"2006","journal-title":"Pain Physician"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12249"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/pme.12892"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010017\u20100710\u20103"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967\u2010017\u20101300\u2010y"},{"key":"e_1_2_13_30_1","first-page":"E1189","article-title":"Clinical evaluation and magnetic resonance imaging assessment of intradiscal methylene blue injection for the treatment of discogenic low back pain","volume":"19","author":"Zhang X","year":"2016","journal-title":"Pain Physician"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmrj.2015.08.010"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rehab.2013.01.006"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010006\u20100301\u2010y"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010006\u20100076\u20101"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304\u20103959(94)90007\u20108"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632\u2010199509000\u201000011"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/ldp052"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.166.1.3336678"},{"key":"e_1_2_13_39_1","volume-title":"Pharmacokinetics in Drug Development: Advances and Applications","author":"Brindey CL","year":"2011"},{"key":"e_1_2_13_40_1","unstructured":"Pfizer.Zyvox 600 mg Film\u2010Coated Tablets. Summary of product characteristics (SmPC) \u2013 (emc).2021Accessed September 9 2021.https:\/\/www.medicines.org.uk\/emc\/medicine\/9857#gref"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250210158249"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11091193"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.12.3789\u20103794.2003"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000333"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3484\u20103489.2002"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.70009","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T11:17:05Z","timestamp":1735211825000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.70009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,14]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/jsp2.70009"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.70009","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,14]]},"assertion":[{"value":"2024-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70009"}}