当前位置： SCI文献检索 > JOURNAL OF PHARMACEUTICAL SCIENCES期刊下所有文献 > Pharmacokinetics and tissue distribution after intravenous administration of a single dose of amphotericin B cochleates, a new lipid-based delivery system.

Pharmacokinetics and tissue distribution after intravenous administration of a single dose of amphotericin B cochleates, a new lipid-based delivery system.

Abstract：

:Model independent pharmacokinetic analysis of intravenous (iv) amphotericin B cochleates (CAMB), a new lipid-based drug delivery system, in mice (0.625 mg/kg) shows a two-phase disposition profile in blood [area under the curve of concentration versus time from time zero to infinity (AUC(0-infinity)) = 1.01 microg. h/mL, half-life (t((1/2))) = 11.68 h, volume of distribution at steady state (V(ss)) = 9.59 L/kg, clearance (CL) = 10.36 mL/min/kg and mean residence time from time 0 to infinity (MRT(0-infinity)) = 15.41 h). In target tissues, maximum time (t(max)) ranged from 2 min (spleen and lung) to 10 min (liver) and lungs presented the highest AMB concentration (16.4 microg. h/g) followed by liver (8.56 microg/g), and spleen (6.63 microg/g). In addition, liver and spleen presented the longest elution half-life (75.03 and 66.71 h, respectively), MRT(0-infinity) (98.4 and 86.3 h, respectively), and AMB exposure:liver AUC(0-infinity) = 474 and 116.4 microg. h/g for the spleen. The large V(ss) and the extensive tissue AUC indicate large and efficient ability of cochleates to penetrate and deliver AMB. Differences in tissue uptake mechanism and pharmacokinetic data suggest a crucial role of macrophages in CAMB clearance from blood as well as an essential role of the liver and the spleen in AMB distribution to target tissues.

journal_name

J Pharm Sci

journal_title

Journal of pharmaceutical sciences

authors

Segarra I,Movshin DA,Zarif L

doi

10.1002/jps.10173

subject

Has Abstract

pub_date

2002-08-01 00:00:00

pages

1827-37

issue

8

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)31051-6

journal_volume

91

pub_type

杂志文章

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