title: Development of a sustained-release recombinant human growth hormone formulation.
abstract: Recombinant human growth hormone (rhGH) therapy for short stature must be administered as a daily injection because of its poor bioavailability and short half-life. In the present study, a sustained-release formulation of rhGH (SR-rhGH), DA-3003, was prepared using double emulsion solvent evaporation with poly(D,L-lactide-co-glycolide) (PLGA), zinc oxide and hydroxypropyl-beta-cyclodextrin (HPCD) as the release modulator, stabilizer, and aggregation-prevention agent, respectively. After a single administration of DA-3003, the elevated concentration of rhGH in plasma was sustained for 14 days in rats and 28 days in monkeys. The plasma concentration of insulin-like growth factor-1 (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), which are pharmacodynamic markers of rhGH administration, increased and remained elevated for approximately 28 days in monkeys. Monkeys administered DA-3003 did not develop antibodies to hGH, indicating safety of the SR-rhGH formulation comparable to that observed with daily rhGH injections (Growtropin II). There were no significant differences in efficacy between Growtropin II (daily dose of 5 microg/animal for 14 days) and DA-3003 (weekly dose of 35 microg/animal for 14 days with a dosing interval of a week) in hypophysectomized rats, as assessed by changes in body weight and the width of the tibial growth plate. These results show that a sustained-release rhGH formulation, DA-3003, has the potential to be used safely and efficaciously in a weekly dosing regimen.
authors.affiliation: Biopharmaceutical Research Laboratory, Dong-A Pharm. Co. Ltd., Gyeonggi, 446-905, Republic of Korea.
authors.forename: H H
authors.initials: HH
authors.lastname: Kwak
authors.forename: W S
authors.initials: WS
authors.lastname: Shim
authors.forename: M K
authors.initials: MK
authors.lastname: Choi
authors.forename: M K
authors.initials: MK
authors.lastname: Son
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Yang
authors.forename: T H
authors.initials: TH
authors.lastname: Kim
authors.forename: G I
authors.initials: GI
authors.lastname: Lee
authors.forename: B M
authors.initials: BM
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Kang
authors.forename: C K
authors.initials: CK
authors.lastname: Shim