title: Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor in children after intravenous and subcutaneous administration.
abstract: Despite its widespread use, only limited pharmacokinetic data exist for recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), especially in children. We evaluated the pharmacokinetics of rhGM-CSF in children who had undergone intensive multiagent chemotherapy: 11 children with refractory solid tumors received 500-1500 micrograms/m2 of rhGM-CSF (sargramostim) as a daily 2-h intravenous (iv) infusion, and seven children received subcutaneous (sc) rhGM-CSF at 1500-2000 micrograms/m2/d in two daily injections for 2 weeks. Serum samples obtained before and after rhGM-CSF administration were analyzed for granulocyte-macrophage colony-stimulating factor (GM-CSF) by a bioassay and by ELISA. Concentrations measured by the two methods were highly correlated (r2 = 0.89, p < 0.001). Following 2-h iv infusions, the concentration-time data were best described by a two-compartment, first-order elimination model. The median (range) for rhGM-CSF systemic clearance (CI) was 49 mL/min/m2 (range, 15-118 mL/min/m2), terminal half-life (t1/2) was 1.6 h (range, 0.9-2.5 h), and the time the GM-CSF concentration was > 1 ng/mL was 9 h (range, 6-13 h). The CI was not dose dependent or related to patient age. The absolute neutrophil count day 14 of GM-CSF was significantly related to GM-CSF dosage and platelet count on day 1. There was a weak correlation between AUC and duration of neutropenia (p = 0.05). The sc concentration-time data were best described by a one-compartment model with first-order absorption and elimination. Median apparent clearance was 72 mL/min/m2 (range, 27-231 mL/min/m2) and t1/2 was 2.3 h (range 0.7-3.8 h).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pharmaceutical, Department, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: N
authors.initials: N
authors.lastname: Stute
authors.forename: W L
authors.initials: WL
authors.lastname: Furman
authors.forename: M
authors.initials: M
authors.lastname: Schell
authors.forename: W E
authors.initials: WE
authors.lastname: Evans
mesh_terms: D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D010599:Pharmacokinetics; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D011995:Recombination, Genetic; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013936:Thymidine