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Titolo:
Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects
Autore:
Igarashi, T; Ogata, E; Maruyama, K; Fukuda, T; Azuma, J;
Indirizzi:
Univ Tokyo, Branch Hosp, Dept Internal Med, Bunkyo Ku, Tokyo 1128688, Japan Univ Tokyo Tokyo Japan 1128688 rnal Med, Bunkyo Ku, Tokyo 1128688, Japan Canc Inst Hosp, Tokyo 1708455, Japan Canc Inst Hosp Tokyo Japan 1708455Canc Inst Hosp, Tokyo 1708455, Japan Osaka Pharmacol Res Clin, Osaka 5650853, Japan Osaka Pharmacol Res Clin Osaka Japan 5650853 Clin, Osaka 5650853, Japan Osaka Univ, Grad Sch Pharmaceut Sci, Osaka 5650871, Japan Osaka Univ Osaka Japan 5650871 Sch Pharmaceut Sci, Osaka 5650871, Japan
Titolo Testata:
ENDOCRINE JOURNAL
fascicolo: 5, volume: 47, anno: 2000,
pagine: 517 - 523
SICI:
0918-8959(200010)47:5<517:EOCAKO>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
CALCIUM-SENSING RECEPTOR; PARATHYROID-HORMONE; HYPERPARATHYROIDISM; EXPRESSION; METABOLISM; INHIBITION; ALLELE;
Keywords:
calcimimetics; calcium-sensing receptor; gastrin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
19
Recensione:
Indirizzi per estratti:
Indirizzo: Igarashi, T Univ Tokyo, Branch Hosp, Dept Internal Med, Bunkyo Ku, 3-28-6 Mejirodai, Tokyo 1128688, Japan Univ Tokyo 3-28-6 Mejirodai Tokyo Japan 1128688 128688, Japan
Citazione:
T. Igarashi et al., "Effect of calcimimetic agent, KRN568, on gastrin secretion in healthy subjects", ENDOCR J, 47(5), 2000, pp. 517-523

Abstract

KRN568 is a calcimimetic compound which acts on the calcium sensing receptors (CaR) on the parathyroid gland to suppress secretion of PTH. A recent report has demonstrated that CaRs are expressed on cultured human antral gastrin cells and that gastrin secretion is stimulated by an increase in extracellular calcium level. However, the effect of KRN568 on serum gastrin levels has yet to be clinically assessed. We therefore studied the effect of this calcimimetic on gastrin secretion in healthy subjects enrolled in the phase 1 study for KRN568 currently carried out in Japan. Single doses of KRN568, ranging from 25 mg to 400 mg, were orally administered to 6 healthy male volunteers at fasting and after meal. One subject proved to be a poor metabolizer (PM) for this compound and showed more than 10-fold high concentrations of plasma KRN568 (fasting Cmax 90.8 and non-fasting 83.8 ng/ml) compared to the other 5 individuals (Cmax 6.5 +/- 2.2 and 7.4 +/- 1.6 ng/ml, respectively). Plasma gastrin levels showed mild but apparent increase (from 30 to 125 pg/ml) in this particular subject, while there were no significantincreases in the other five people (from 34+/-6 to 63+/-3 pg/ml) after oral administration of 400 mg KRN568 at fasting. In the PM, administration of KRN568 resulted in extraordinarily high serum drug levels associated with transient increase of gastrin levels. This observation suggested that calcium-induced stimulation of gastrin secretion in human was mediated by a mechanism involving CaR. Potential side effects related to the increased gastrinsecretion may be warranted in the practical use of this compound.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 23:49:45