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Pharmacokinetics and splenic accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide after a single administration to rats.

Hua, Jianyi LU ; Sheng, Yezhou LU ; Olin, Magnus; Pero, Ronald LU and Edvardsen, Klaus LU (2004) In Biopharmaceutics & Drug Disposition 25(7). p.313-322
Abstract
The purpose of this study was to measure the pharmacokinetics and tissue accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide (NACPA) after oral or intravenous administration at a single dose of 25 mg/kg to female W/Fu rats. The serum pharmacokinetics of NACPA were characterized by rapid absorption, distribution and elimination. However, in comparison with its parent compound, 4-amino-3-chloro-N-(2-diethylamino-ethyl) benzamide (3-CPA), NACPA displayed a higher Cmax (mean+/-SD, 201+/-21 vs 33.6+/-0.5 nmol/ml, p < 0.05), and a longer elimination half-life (50+/-0.8 vs 36.6+/-1.1 min, p < 0.05) following intravenous administration. Bioavailability of NACPA was significantly greater than that of 3-CPA (50% compared... (More)
The purpose of this study was to measure the pharmacokinetics and tissue accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide (NACPA) after oral or intravenous administration at a single dose of 25 mg/kg to female W/Fu rats. The serum pharmacokinetics of NACPA were characterized by rapid absorption, distribution and elimination. However, in comparison with its parent compound, 4-amino-3-chloro-N-(2-diethylamino-ethyl) benzamide (3-CPA), NACPA displayed a higher Cmax (mean+/-SD, 201+/-21 vs 33.6+/-0.5 nmol/ml, p < 0.05), and a longer elimination half-life (50+/-0.8 vs 36.6+/-1.1 min, p < 0.05) following intravenous administration. Bioavailability of NACPA was significantly greater than that of 3-CPA (50% compared with 14%, p < 0.05). The tissue accumulation of NACPA was generally higher than that of 3-CPA. NACPA was deposited at higher concentrations in the spleen than in the kidney and liver. Cellular pharmacokinetics indicated that NACPA accumulated more readily in lymphocyte related cells than in liver related cells. Furthermore, incubation of human peripheral lymphocytes with NACPA resulted in inhibition of lymphocyte proliferation, INF-gamma production and chemotaxis. All these results suggest that NACPA may be a good candidate drug for oral administration for immune modulation (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
benzamide, pharmacokinetics, tissue distribution, lymphocyte activity
in
Biopharmaceutics & Drug Disposition
volume
25
issue
7
pages
313 - 322
publisher
John Wiley & Sons
external identifiers
  • pmid:15386479
  • wos:000224663200005
  • scopus:6444222079
ISSN
0142-2782
DOI
10.1002/bdd.414
language
English
LU publication?
yes
id
0a389d34-28cf-459b-b322-6a4eb819dce2 (old id 127226)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15386479&dopt=Abstract
date added to LUP
2007-07-13 13:58:13
date last changed
2017-01-01 05:13:30
@article{0a389d34-28cf-459b-b322-6a4eb819dce2,
  abstract     = {The purpose of this study was to measure the pharmacokinetics and tissue accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide (NACPA) after oral or intravenous administration at a single dose of 25 mg/kg to female W/Fu rats. The serum pharmacokinetics of NACPA were characterized by rapid absorption, distribution and elimination. However, in comparison with its parent compound, 4-amino-3-chloro-N-(2-diethylamino-ethyl) benzamide (3-CPA), NACPA displayed a higher Cmax (mean+/-SD, 201+/-21 vs 33.6+/-0.5 nmol/ml, p &lt; 0.05), and a longer elimination half-life (50+/-0.8 vs 36.6+/-1.1 min, p &lt; 0.05) following intravenous administration. Bioavailability of NACPA was significantly greater than that of 3-CPA (50% compared with 14%, p &lt; 0.05). The tissue accumulation of NACPA was generally higher than that of 3-CPA. NACPA was deposited at higher concentrations in the spleen than in the kidney and liver. Cellular pharmacokinetics indicated that NACPA accumulated more readily in lymphocyte related cells than in liver related cells. Furthermore, incubation of human peripheral lymphocytes with NACPA resulted in inhibition of lymphocyte proliferation, INF-gamma production and chemotaxis. All these results suggest that NACPA may be a good candidate drug for oral administration for immune modulation},
  author       = {Hua, Jianyi and Sheng, Yezhou and Olin, Magnus and Pero, Ronald and Edvardsen, Klaus},
  issn         = {0142-2782},
  keyword      = {benzamide,pharmacokinetics,tissue distribution,lymphocyte activity},
  language     = {eng},
  number       = {7},
  pages        = {313--322},
  publisher    = {John Wiley & Sons},
  series       = {Biopharmaceutics & Drug Disposition},
  title        = {Pharmacokinetics and splenic accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide after a single administration to rats.},
  url          = {http://dx.doi.org/10.1002/bdd.414},
  volume       = {25},
  year         = {2004},
}