Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys

Martha C. Sola, Robert D. Christensen, Alan D. Hutson, Alice F Tarantal

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Thrombocytopenia is common among sick neonates. Certain groups of thrombocytopenic adults respond favorably to the administration of recombinant thrombopoietin or to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a recombinant human polypeptide that contains the receptor-binding N-terminal domain of thrombopoietin. The effectiveness and safety of such treatment in neonates, however, have not been reported. The purpose of the present study was to determine the biologic activity and safety of PEG-rHuMGDF administration to newborn rhesus monkeys. Eight monkeys were divided into four groups and treated subcutaneously with 0.00, 0.25, 1.00, or 2.50 μg/kg once daily for 7 d. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates before the first dose and again on d 8. Pharmacokinetic evaluations were performed on the animals that received the highest dose of PEG-rHuMGDF. All monkeys had normal growth during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration occurred at 3 h, and the half-life was 8.4 to 13.0 h. As in adult rhesus monkeys, platelet counts in the treated neonates began to rise on d 6, peaked on d 11, and returned to baseline by d 23. The two highest doses generated an 8- to 12-fold increase in platelets, whereas those treated with 0.25 μg/kg had a 6-fold increase. Other hematologic parameters measured were unaffected. Thus, newborn monkeys responded to doses of PEG- rHuMGDF that were similar to or smaller than (per kilogram body weight) those that are effective in adult animals and did so without obvious short-term toxicity.

Original languageEnglish (US)
Pages (from-to)208-214
Number of pages7
JournalPediatric Research
Volume47
Issue number2
StatePublished - Feb 2000

Fingerprint

Thrombopoietin
Macaca mulatta
Pharmacokinetics
Haplorhini
Safety
Blood Cell Count
Hematopoietic Stem Cells
Serum
Platelet Count
Thrombocytopenia
Half-Life
Blood Platelets
Bone Marrow
Body Weight
Blood Pressure
Peptides
polyethylene glycol-recombinant human megakaryocyte growth and development factor
Growth

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Pharmacokinetics, pharmacodynamics, and safety of administering pegylated recombinant megakaryocyte growth and development factor to newborn rhesus monkeys. / Sola, Martha C.; Christensen, Robert D.; Hutson, Alan D.; Tarantal, Alice F.

In: Pediatric Research, Vol. 47, No. 2, 02.2000, p. 208-214.

Research output: Contribution to journalArticle

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