Abstract：
:The disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222; 1), a potent 5-hydroxytryptamine antagonist, and its N-demethylated and N-oxide metabolites was studied in dogs and monkeys. After single, intravenous doses of 1 at 5 mg/kg, the mean terminal half-lives of 1 in plasma were 2.6 h in the dog and 3.8 h in the monkey. The mean half-life of the N-demethylated metabolite in dogs (approximately 20 h) was very similar to that in monkeys. However, the mean half-life of the N-oxide metabolite in dogs (10.8 h) was different from that in monkeys (3.9 h). The steady-state volume of distribution of 1 was 16 L/kg in dogs and 8.9 L/kg in monkeys. Examination of the mean residence times revealed that 1, in both species, and the N-oxide metabolite, in dogs, distributed to the peripheral tissue, whereas the distribution of the N-demethylated metabolite in both species and the N-oxide metabolite in monkeys was limited mainly to the systemic circulation. Compound 1 was metabolized extensively in both species. In dogs, 0.7, 2.5 and 40.6% of the administered dose were excreted in 0-120-h urine samples as 1 and its N-demethylated and N-oxide metabolites, respectively. In monkeys, however, the corresponding percentages were 0.8, 0.7, and 1.8%. Most of the administered dose in monkeys was excreted in urine as 3,5-dichlorobenzoic acid and its glycine conjugate.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Cheng H,Larsen DL,Ragner JA,Sproles GD,Gordon WPdoi
10.1002/jps.2600810410subject
Has Abstractpub_date
1992-04-01 00:00:00pages
345-7issue
4eissn
0022-3549issn
1520-6017pii
S0022-3549(15)48816-1journal_volume
81pub_type
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更新日期：2017-09-01 00:00:00
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doi：10.1002/jps.2600810625
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doi：10.1002/jps.23326
更新日期：2012-12-01 00:00:00
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abstract：:The essential oil of Teucrium polium, growing in Saudi Arabia, was thoroughly investigated for its constituents by GLC-mass spectrometry, TLC, and spectrophotometric methods. This investigation revealed the presence of 10 terpenoidal compounds including the hydrocarbons beta-pinene, limonene, alpha-phellandrene, and g...
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abstract：:Naltrexone (NTX) is an opioid antagonist used for treatment of narcotic dependence and alcoholism. Transdermal naltrexone delivery is desirable to help improve patient compliance. The purpose of this study was to increase the delivery rate of NTX across human skin by using lipophilic alkyl ester prodrugs. Straight-cha...
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