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Titolo:
Studies on the mechanism of subcellular distribution of basic drugs based on their lipophilicity
Autore:
Ishizaki, J; Yokogawa, K; Ohkuma, S; Ichimura, F; Miyamoto, K;
Indirizzi:
Kanazawa Univ, Sch Med, Dept Hosp Pharm, Kanazawa, Ishikawa 9208641, JapanKanazawa Univ Kanazawa Ishikawa Japan 9208641 wa, Ishikawa 9208641, Japan Kanazawa Univ, Fac Pharmaceut Sci, Dept Mol & Cellular Biol, Kanazawa, Ishikawa 9208641, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9208641 wa, Ishikawa 9208641, Japan
Titolo Testata:
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
fascicolo: 7, volume: 121, anno: 2001,
pagine: 557 - 565
SICI:
0031-6903(200107)121:7<557:SOTMOS>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
JPN
Soggetto:
PHYSIOLOGICAL PHARMACOKINETIC MODEL; TISSUE DISTRIBUTION; RAT-LIVER; PARTITION-COEFFICIENT; IN-VITRO; BIPERIDEN; BRAIN; TRANSPORTER; ELIMINATION; LYSOSOMES;
Keywords:
basic drug; distribution; lysosome; lipophilicity; disposition kinetics;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Miyamoto, K Kanazawa Univ, Sch Med, Dept Hosp Pharm, Kanazawa, Ishikawa 9208641, Japan Kanazawa Univ Kanazawa Ishikawa Japan 9208641 9208641, Japan
Citazione:
J. Ishizaki et al., "Studies on the mechanism of subcellular distribution of basic drugs based on their lipophilicity", YAKUGAKU ZA, 121(7), 2001, pp. 557-565

Abstract

This paper described the studies on the mechanism of subcellular distribution of lipophilic weak bases. Although the tissue distribution of basic drugs appeared to decrease with time simply in parallel with their plasma concentration, their subcellular distribution in various tissues exhibited a variety of patterns. Basic drugs were distributed widely in various tissues, but were concentrated in lung granule fraction, where their accumulation was dependent on their lipophilicity and lysosomal uptake. As the plasma concentration of drugs decreased after maximum level, the contribution of lysosomes to their subcellular distribution increased. The uptake of the basic drugs into lysosomes depended both on their intralysosomal pH and on the drug lipophilicity. As the lipophilicity of the basic drugs increased, they accumulated more than the values predicted from the pH-partition theory and raised the intralysosomal pH more potently, probably owing to their binding with lysosomal membranes with or without additional intralysosomal aggregation. These phenomena should be considered as a basis of drug interaction inclinical treatments.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 03:53:10