{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:30:52Z","timestamp":1777451452405,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T00:00:00Z","timestamp":1500854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Lambert\u2010Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4\u2010diaminopyridine (3,4\u2010DAP) free base is an investigational orphan drug used to treat LEM\u2010related weakness. We performed a population pharmacokinetic\/pharmacodynamic (PK\/PD) analysis using 3,4\u2010DAP and metabolite concentrations collected from a phase II study in patients with LEM. The Triple Timed Up &amp; Go (3TUG) assessment, which measures lower extremity weakness, was the primary outcome measure. A total of 1,270 PK samples (49 patients) and 1,091 3TUG data points (32 randomized patients) were included in the PK\/PD analysis. A two\u2010compartment and one\u2010compartment model for parent and metabolite, respectively, described the PK data well. Body weight and serum creatinine partially explained the variability in clearance for the final PK model. A fractional inhibitory maximum effect (E<jats:sub>max<\/jats:sub>) model characterized the exposure\u2010response relationship well. The PK\/PD model was applied to identify a suggested dosing approach for 3,4\u2010DAP free base.<\/jats:p>","DOI":"10.1002\/psp4.12218","type":"journal-article","created":{"date-parts":[[2017,6,17]],"date-time":"2017-06-17T21:32:44Z","timestamp":1497735164000},"page":"625-634","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetics\/Pharmacodynamics of 3,4\u2010Diaminopyridine Free Base in Patients With Lambert\u2010Eaton Myasthenia"],"prefix":"10.1002","volume":"6","author":[{"given":"Nilay","family":"Thakkar","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey T.","family":"Guptill","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Ale\u0161","sequence":"additional","affiliation":[{"name":"Jacobus Pharmaceutical Company, Inc. 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