Relationship between absolute neutrophil count profiles and pharmacokinetics of DA-3031, a pegylated granulocyte colony-stimulating factor (pegylated-G-CSF): a dose block-randomized, double-blind, dose-escalation study in healthy subjects.
Clin Drug Investig
; 33(11): 817-24, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24078278
ABSTRACT
BACKGROUND:
DA-3031 is a newly developed pegylated filgrastim, a recombinant human granulocyte colony-stimulating factor, that is expected to have an extended duration of action compared with non-modified filgrastim.OBJECTIVE:
This study evaluated the tolerability, pharmacokinetics, and pharmacodynamics of DA-3031 in humans, and compared them with filgrastim.METHODS:
The study was conducted in 48 healthy male Korean subjects. Forty subjects received subcutaneous single doses of 1.8, 3.6, 6, or 18 mg of DA-3031 or placebo in a dose block-randomized, double-blind, dose-escalation design. The remaining eight subjects were given subcutaneous doses of 100 µg/m² of filgrastim daily for 5 days. Serial blood samples were collected for pharmacokinetic and pharmacodynamic analyses up to 312 h after the administration of DA-3031 and up to 264 h following the first administration of filgrastim.RESULTS:
DA-3031 reached its peak plasma concentration at 6.0-48.0 h and was eliminated mono-exponentially. The pharmacokinetic parameters of DA-3031 increased with dose in a non-linear fashion. Absolute neutrophil count (ANC) levels increased with the dose of DA-3031, although the extent of the increase in ANC decreased at higher dose levels. DA-3031 resulted in similar ANC changes in the 3.6 to 6 mg dose range as 100 µg/m² of filgrastim. The most frequent adverse event was back pain, which was observed after both DA-3031 and filgrastim administration.CONCLUSIONS:
DA-3031 showed non-linear pharmacodynamic and pharmacokinetic profiles and an extended duration of action compared with non-modified filgrastim, without unexpected toxicities in healthy subjects.
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Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Fator Estimulador de Colônias de Granulócitos
/
Contagem de Leucócitos
/
Neutrófilos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Clin Drug Investig
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2013
Tipo de documento:
Article