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Titolo:
3RD-GENERATION MODEL FOR CORTICOSTEROID PHARMACODYNAMICS - ROLES OF GLUCOCORTICOID RECEPTOR MESSENGER-RNA AND TYROSINE AMINOTRANSFERASE MESSENGER-RNA IN RAT-LIVER
Autore:
XU ZX; SUN YN; DUBOIS DC; ALMON RR; JUSKO WJ;
Indirizzi:
HOFFMANN LA ROCHE INC NUTLEY NJ 07110 SUNY BUFFALO,SCH PHARM,DEPT PHARMACEUT BUFFALO NY 14260 SUNY BUFFALO,DEPT BIOL SCI BUFFALO NY 14260
Titolo Testata:
Journal of pharmacokinetics and biopharmaceutics
fascicolo: 2, volume: 23, anno: 1995,
pagine: 163 - 181
SICI:
0090-466X(1995)23:2<163:3MFCP->2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
HORMONE MESSENGER-RNA; PREDNISOLONE PHARMACODYNAMICS; RIBONUCLEIC-ACID; METHYLPREDNISOLONE; EXPRESSION; CELLS; TRAFFICKING; STABILITY;
Keywords:
METHYLPREDNISOLONE; PHARMACOKINETICS; PHARMACODYNAMICS; GLUCOCORTICOID RECEPTOR; TYROSINE AMINOTRANSFERASE; NORTHERN HYBRIDIZATION; MESSENGER-RNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
Z.X. Xu et al., "3RD-GENERATION MODEL FOR CORTICOSTEROID PHARMACODYNAMICS - ROLES OF GLUCOCORTICOID RECEPTOR MESSENGER-RNA AND TYROSINE AMINOTRANSFERASE MESSENGER-RNA IN RAT-LIVER", Journal of pharmacokinetics and biopharmaceutics, 23(2), 1995, pp. 163-181

Abstract

A third-generation pharmacokinetic/pharmacodynamic model was proposedfor receptor/genemediated corticosteroid effects. The roles of the messenger RNA (mRNA) for the glucocorticoid receptor (GR) in hepatic GR down-regulation and the MRNA for hepatic tyrosine aminotransferase (TAT) induction by methylprednisolone (MPL) were examined. Male adrenalectomized Wistar rats received 50 mg/kg MPL iv. Blood and liver samples were collected at various time points for a period of 18 hr. Plasma concentrations of MPL, free hepatic cytosolic GR densities, GR mRNA, TATmRNA, and tat activities in liver were determined. Plasma MPL profilewas biexponential with a terminal T-1/2 of 0.57 hr. Free hepatic GR density rapidly disappeared from cytoplasm after the MPL dose and then slowly returned to about 60% of starting level after 16 hr. Meanwhile,GR mRNA level fell to 45% of baseline within 2 hr, reached a maximum at about 5 hr, and declined to baseline by 14 hr. TAT induction followed a similar pattern, except the induction was delayed about 0.5 hr. Pharmacodynamic parameters were obtained by fitting seven differential equations in a piecewise fashion. The cascade of corticosteroid steps were modeled by a series of inductions for steroid-receptor-DNA complex, two intermediate transit compartments, TAT mRNA, and TAT activity. Results indicate that GR mRNA and TAT mRNA are major controlling factors for the receptor/gene-mediated effects of corticosteroids.

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Documento generato il 22/10/20 alle ore 03:29:09