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Pharmacokinetic and pharmacodynamic studies of subcutaneously administered recombinant human interleukin‐3 following chemotherapy for non‐Hodgkin's lymphoma
Author(s) -
Hovgaard D. J.,
Mortensen B. T.,
Nissen N. I.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05305.x
Subject(s) - pharmacokinetics , medicine , pharmacodynamics , lymphoma , pharmacology , chemotherapy
Summary. The pharmacokinetics and the pharmacodynamic profile of subcutaneously administered recombinant human non‐glycosylated interleukin‐3 (rhIL‐3) was studied in lymphoma patients after standard CHOP chemotherapy. 30 patients received 0.5, 1.0, 5.0, 7.5 and 10/ig/kg (six patients at each dose level) of rhIL‐3 for 14 d. Serum rhIL‐3 samples were obtained regularly during the treatment and serially over a 24 h period on the first (cycle day 2) and the last (cycle day 15) day of rhIL‐3 treatment for pharmacokinetic evaluation. Following s.c. injection on cycle day 2, the maximum rhIL‐3 serum concentration ranged from 289pg/ml (0‐5/ig/kg) to 4690pg/ml (10/xg/kg). Both the maximum serum concentration ( R = 0.90, P < 0.0001) and the area under the serum concentration‐time curve ( R = 0.95, P < 0.0001) were related to dose. The elimination half‐life T 1/2 β was 160 min for 0.5 μg/kg and 134 min for 10μg/kg, with no apparent dose relationship. The systemic clearance of 3.0–6.0ml/min/kg was comparable at all dose levels. No significant difference was noted between pharmacokinetic parameters on the first day of rhIL‐3 and the last day of treatment, and no accumulation of the drug was noted throughout the study. The pharmacokinetic parameters correlated poorly to the clinical response of the growth factor, where dose in μg/kg seemed to be the most important single factor.