Pharmacokinetics and splenic accumulation of N-acetylamino-3-chloro-N-(2-diethylamino-ethyl) benzamide after a single administration to rats.
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.
Hua
Jianyi
J
Department of Cell and Molecular Biology, Section for Tumor Immunology, University of Lund, 221 84, Sweden. Jianyi.Hua@tumor.lu.se
Sheng
Yezhou
Y
Olin
Magnus
M
Pero
Ronald
R
Edvardsen
Klaus
K
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013154:Spleen / Q000378:metabolism*
D001549:Benzamides; C495135:N-acetylamino-3-chloro-N-(2-diethylaminoethyl)benzamide