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Titolo:
A pharmacokinetic pharmacodynamic model for recombinant human growth hormone effects on induction of insulin-like growth factor I in monkeys
Autore:
Sun, YN; Lee, HJ; Almon, RR; Jusko, WJ;
Indirizzi:
SUNY Buffalo, Sch Pharm, Dept Pharmaceut, Buffalo, NY 14260 USA SUNY Buffalo Buffalo NY USA 14260 Dept Pharmaceut, Buffalo, NY 14260 USA SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA SUNY Buffalo Buffalo NY USA 14260 o, Dept Biol Sci, Buffalo, NY 14260 USA Alkermes Inc, Cambridge, MA USA Alkermes Inc Cambridge MA USAAlkermes Inc, Cambridge, MA USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 289, anno: 1999,
pagine: 1523 - 1532
SICI:
0022-3565(199906)289:3<1523:APPMFR>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
IGF-BINDING-PROTEINS; (GH)-BINDING PROTEIN; HYPOPHYSECTOMIZED RATS; DEFICIENT CHILDREN; HUMAN GH; SERUM; PURIFICATION; EXPRESSION; RESPONSES; INJECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Jusko, WJ SUNY Buffalo, Sch Pharm, Dept Pharmaceut, 565 Hochstetter Hall, Buffalo, NY SUNY Buffalo 565 Hochstetter Hall Buffalo NY USA 14260 ffalo, NY
Citazione:
Y.N. Sun et al., "A pharmacokinetic pharmacodynamic model for recombinant human growth hormone effects on induction of insulin-like growth factor I in monkeys", J PHARM EXP, 289(3), 1999, pp. 1523-1532

Abstract

The pharmacokinetics of recombinant human growth hormone (rhGH) and its effects on the induction of insulin-like growth factor I (IGF-I) were studiedin juvenile rhesus monkeys. Disposition profiles of rhGH from two short-term i.v. infusion studies were described by a two-compartment model yieldinga clearance of 16.1 ml/min and T-1/2 of 2.0 h. Four rhGH treatment groups were included in this study: group A, ProLease rhGH (24 mg), a sustained-release microsphere formulation; group B, a single s.c. injection plus an implanted osmotic pump (24.4 mg); group C, a single s.c. injection (25.9 mg); group D, daily 0.86-mg s.c. injection for 28 days. Their rhGH input profiles were analyzed by a numerical deconvolution method. ProLease and osmotic pump provided zero-order inputs of rhGH and maintained the serum rhGH concentrations around 9 to 13 ng/ml for 16 (group A) and 30 days (group B), For s.c. injections, rhGH underwent first-order absorption. An indirect responsemodel was applied based on use of a Hill function for stimulation of IGF-Iproduction. Parameter values obtained included S-max = 2.2, SC50 = 6.5 ng/ml, and gamma (slope coefficient) = 6.8, which were applicable to all treatments. The area under effect curve showed group B to be most effective for IGF-I induction, whereas group A produced the highest peak level in 16 days. Group C had the lowest induction among the four groups, despite being given the highest dose. Group D had modest IGF-I induction, but the pulsatile rhGH input is less effective than continuous input provided by ProLease. Our pharmacokinetic/pharmacodynamjc model demonstrates that ProLease and osmotic pump delivery were best able to maintain rhGH level above the s.c.(50) value, which provided more effective IGF-I induction compared with the single or daily subcutaneous injections in solution.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 15:03:26