Pharmacokinetics and splenic accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide after a single administration to rats.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/127226
- author
- Hua, Jianyi LU ; Sheng, Yezhou LU ; Olin, Magnus ; Pero, Ronald LU and Edvardsen, Klaus LU
- organization
- publishing date
- 2004
- 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 Inc.
- 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
- 2016-04-01 12:31:49
- date last changed
- 2022-01-27 06:21:55
@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 < 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}}, author = {{Hua, Jianyi and Sheng, Yezhou and Olin, Magnus and Pero, Ronald and Edvardsen, Klaus}}, issn = {{0142-2782}}, keywords = {{benzamide; pharmacokinetics; tissue distribution; lymphocyte activity}}, language = {{eng}}, number = {{7}}, pages = {{313--322}}, publisher = {{John Wiley & Sons Inc.}}, 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}}, doi = {{10.1002/bdd.414}}, volume = {{25}}, year = {{2004}}, }