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Clinical pharmacokinetic studies with INN 00835 (Nemifitide), a novel pentapeptide antidepressant
Author(s) -
Feighner John P.,
Nicolau Gabriela,
Abajian Henry,
Marricco Nadia Cardillo,
Morrison John,
Sverdlov Lev,
Hlavka Joseph,
Tonelli George,
Spirito Carlo Di,
Faria George
Publication year - 2002
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.290
Subject(s) - pharmacokinetics , adverse effect , medicine , pharmacology , dosing , drug , antidepressant , clinical trial , hippocampus
Nemifitide (4‐fluoro‐L‐phenylalanyl‐trans‐4‐hydroxy‐L‐prolyl‐L‐arginylglycyl‐L‐tryptophanamide ditrifluoroacetate) is a novel antidepressant, currently in phase 2/3 clinical trials. The purpose of our phase 1 clinical trials (conducted over a three year period) was to provide safety and pharmacokinetic data to support its clinical development as an antidepressant drug. Single and multiple doses ranging from 18 to 320 mg were administered subcutaneously to healthy volunteers in five phase 1 studies. Plasma concentrations of unchanged parent drug were determined by a validated LC/MS/MS method in blood samples collected at timepoints between 10 min and 72 h after dosing. Nemifitide was rapidly absorbed ( C max at 10 min) and eliminated ( t 1/2 15–30 min) in most subjects. Regression and power model analyses were used to evaluate the data. The results indicate that pharmacokinetic parameters: AUC 0− t , AUC 0−∞ and C max , were close to dose proportional in the dose range investigated. There was no evidence of systemic accumulation of drug following 5 daily doses. No serious adverse events or clinically significant systemic adverse events occurred at any of the doses investigated in the over 100 subjects dosed in these studies. Drug‐related adverse events were limited to local and transient skin reactions (pain and/or erythema) at the injection site, especially at the high doses administered: 240 and 320 mg. Copyright © 2002 John Wiley & Sons, Ltd.