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Pharmacokinetics (PK) and pharmacodynamics (PD) of palifermin (PAL) (a R‐HUKGF molecule)
Author(s) -
ZiaAmirhosseini P.,
Salfi M.,
Yates W.,
Gillespie B.,
Leese P.,
Rohwer R.,
Sullivan J.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.067
Subject(s) - medicine , pharmacodynamics , mucositis , pharmacokinetics , placebo , pharmacology , cmax , urology , gastroenterology , toxicity , pathology , alternative medicine
Background/Aims PAL has been shown in hematological cancer patients to reduce the duration, incidence, and severity of mucositis following 3‐consecutive daily doses of 60 ug/kg. In the studies described here, the PK/PD of PAL was evaluated. Methods In 2, randomized, double‐blind, placebo‐controlled, dose escalation studies, healthy subjects received single (SL) (60–250 ug/kg) or multiple (MP) (40 ug/kg/day[d] × 3d) IV doses of PAL or placebo. PK and PD (Ki67 staining on buccal mucosa biopsies) assessments were conducted at baseline and postdose. Results 75 subjects (18–63 yrs) received PAL. Exposure to PAL increased approximately dose proportionally (3‐fold increase in C 0 and AUC for a 4‐fold increase in dose). An increased PD response was observed with increased dose, with an apparent flattening of the dose response relationship at higher doses. The PD response 24 hrs after the 3 rd MP dose of 40 ug/kg was similar to that at 48 hrs after a SL dose of 120 ug/kg. Conclusions A SL collapsed dose yields comparable PD to the same total dose partitioned over 3 consecutive days. Based on the safety, PD, and efficacy profiles of PAL, future oncology trials will be conducted using a SL 180 ug/kg dose in lieu of 3 doses at 60 ug/kg. Clinical Pharmacology & Therapeutics (2005) 77 , P17–P17; doi: 10.1016/j.clpt.2004.11.067