Abstract：
:Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotransformation, several organs should have the ability to metabolize DTZ, however it is still assumed that the liver is the only organ implicated in its elimination. In this study, the fate of DTZ, MA and M1 was assessed in several organs that could contribute to their biotransformation. To this purpose, DTZ (48.2 microM) was incubated in the 10,000 x g supernatant of homogenates of rabbit tissues for 60 min at 37 degrees C. Multiple samples were withdrawn, and DTZ and its metabolites were assayed by HPLC. The elimination rate constant of DTZ in 10,000 x g supernatants varied between the organs: liver 334 +/- 45, proximal small intestine 69 +/- 11, distal small intestine 25 +/- 3, lungs 15 +/- 6 and kidneys 8 +/- 6 (10(-4) min-1). The metabolism of DTZ in the liver generated large amounts of MA but no M1, and in the small intestine, modest amounts of both metabolites. When MA (50.0 microM) or M1 (53.7 microM) were incubated in liver homogenates, the estimated elimination rate constant were 166 +/- 23 and 468 +/- 53 (10(-4) min-1), respectively. The rate of degradation of the metabolites in the small intestine was much slower.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Homsy W,Lefebvre M,Caillé G,du Souich Pdoi
10.1023/a:1016226601988subject
Has Abstractpub_date
1995-04-01 00:00:00pages
609-14issue
4eissn
0724-8741issn
1573-904Xjournal_volume
12pub_type
杂志文章abstract：PURPOSE:S-(4-Nitrobenzyl)-6-thioinosine (NBMPR) is routinely used at concentrations of 0.10 μM and 0.10 mM to specifically inhibit transport of nucleosides mediated by equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2), respectively. We recently showed that NBMPR (0.10 mM) might also inhibit placental active e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9094-2
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1991-10-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1992-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
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更新日期：1994-01-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1992-01-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：1984-01-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2006-03-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2004-06-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2014-10-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2008-05-01 00:00:00
abstract：PURPOSE:The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND METHODS...
journal_title：Pharmaceutical research
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更新日期：2015-06-01 00:00:00
abstract：PURPOSE:The aim of this study was to test the ability of paclitaxel-loaded poly(butylcyanoacrylate) (PBCA) nanoparticles to overcome multidrug resistance (MDR) in human ovarian resistant cells (A2780/T) and investigate its possible mechanism. METHODS:We prepared paclitaxel-loaded PBCA nanoparticles by interfacial poly...
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