Pharmacokinetics of palifermin administered as the standard dose and as a collapsed dose in patients with hematologic malignancies.
OBJECTIVE
To assess the pharmacokinetic profile of palifermin after intravenous dosing with either a collapsed dose of 180 microg/kg/day for 1 day or a standard dose of 60 microg/kg/day for 3 days, before and after myeloablative chemoradiotherapy and peripheral blood progenitor cell (PBPC) transplantation.


METHODS
Prospective, open-label pharmacokinetic study.


METHODS
University-affiliated hematology and oncology center.


METHODS
Twenty-five adult patients with hematologic malignancies receiving myeloablative therapy; 13 were in the standard-dose group, and 12 were in the collapsed-dose group.


METHODS
Patients received total-body irradiation (study days -8 to -5), etoposide (day -4), cyclophosphamide (day -2), and PBPC transplantation (day 0). Standard-dose palifermin was administered on days -11, -10, -9, 0, 1, and 2; collapsed-dose palifermin was administered on days -11 and 0.


RESULTS
Baseline demographic and clinical characteristics were recorded. Blood samples were obtained for pharmacokinetic assessment, presence of palifermin antibodies, and routine chemistry and hematology panels. Adverse events were documented daily. For both dosing groups, palifermin concentrations declined rapidly (>or= 98%) in the first 30 minutes and increased slightly between 1 and 4 hours after dosing, with a terminal decay phase. For standard-dose palifermin, mean values for area under the serum concentration-time curve (AUC) were within 15% between doses 1 and 3 and within 1% between doses 1 and 4. For collapsed-dose palifermin, mean AUC values and other pharmacokinetic parameters were within 2% between doses 1 and 2. Mean AUC on days -11 and 0 were approximately 4-fold higher for collapseddose palifermin than for standard-dose palifermin. Both dosing regimens were well tolerated.


CONCLUSIONS
Our results were consistent with approximately dose-linear pharmacokinetics for the two dosing regimens, with no observed accumulation. A randomized, controlled study is warranted to assess the safety and efficacy of collapsed-dose palifermin, which may provide a more convenient administration schedule.
Zia-Amirhosseini
Parnian
P
Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, California 91320, USA. pzia@amgen.com
Hurd
David D
DD
Salfi
Margaret
M
Cheah
Tsui Chern
TC
Aycock
Jeffrey
J
Cesano
Alessandra
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019540:Area Under Curve; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006207:Half-Life; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D036102:Peripheral Blood Stem Cell Transplantation; D013997:Time Factors; D014916:Whole-Body Irradiation / Q000379:methods
D051523:Fibroblast Growth Factor 7