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Titolo:
PHARMACOKINETIC CHARACTERIZATION OF MENAQUINONE-4 IN DOGS BY SENSITIVE HPLC DETERMINATION
Autore:
SANO Y; TADANO K; KIKUCHI K; KANEKO K; YUZURIHA T;
Indirizzi:
EISAI & CO LTD,TSUKUBA RES LABS TSUKUBA 30026 JAPAN
Titolo Testata:
Journal of nutritional science and vitaminology
fascicolo: 6, volume: 39, anno: 1993,
pagine: 555 - 566
SICI:
0301-4800(1993)39:6<555:PCOMID>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; GAMMA-CARBOXYGLUTAMIC ACID; K-DEPENDENT CARBOXYLASE; VITAMIN-K; FLUORESCENCE DETECTION; FLUOROMETRIC DETECTION; COLONIC ABSORPTION; PLASMA; RATS; PROTHROMBIN;
Keywords:
MENAQUINONE-4; VITAMIN-K; PHARMACOKINETICS; DOGS; ORAL; BIOAVAILABILITY; FLUORESCENCE DETECTION; OSTEOPOROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
Y. Sano et al., "PHARMACOKINETIC CHARACTERIZATION OF MENAQUINONE-4 IN DOGS BY SENSITIVE HPLC DETERMINATION", Journal of nutritional science and vitaminology, 39(6), 1993, pp. 555-566

Abstract

A simple and sensitive assay method for a pharmacokinetic study of Menaquinone-4 in dogs was established using HPLC with fluorescence detection following extraction with organic solvent. The quantification limit of this method was 1 ng/ml of plasma. A new oily solution formulation of Menaquinone-4 was administered orally to non-fasted dogs at doses of 0.4, 4 and 40 mg/kg. The plasma concentrations reached maximum levels at 1 to 1.5 h after dosing, and then decreased slowly. AUC valuesup to 24 h after administration were almost dose-proportional. Menaquinone-4 was also administered to dogs in soft-capsules, for comparisonwith a conventional hard-capsule oral formulation and an intravenous lecithin formulation. The mean AUC for oral dosing in the soft-capsuleformulation was 13.5% of that for intravenous dosing in lecithin, andwas 4.6 times higher than that for oral dosing in hard-capsules. Additional dosing in fasted dogs indicated that the AUC in pre-fed dogs was about 4 times higher, suggesting that feeding before giving Menaquinone-4 raises the bioavailability. Overall Menaquinone-4 was absorbed rapidly after administration in non-fasted dogs and dose-proportional bioavailability was obtained among the doses of 0.4 to 40 mg/kg. Higherplasma concentrations were observed after administration in the soft-capsule formulation rather than in the hard-capsule formulation. Thesefindings suggest that the soft-capsule formulation would show a good pharmacokinetic profile for elderly patients with osteoporosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 01:18:55