Metabolic fate of the new anti-ulcer drug enprostil in animals. 2nd communication: whole-body autoradiographic distribution of [3H]-enprostil in rats.
The distribution of radioactivity was studied by whole-body autoradiography in rats after oral or intravenous administration of [3H]-enprostil ((+/-)-11a-15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) at a dose of 23 micrograms/kg. After oral administration to male rats, radioactivity in almost all the tissues and organs reached a peak within 15 min to 1 h. The highest levels of radioactivity were found in the contents of the stomach and intestine. High levels of radioactivity were also observed in the liver and kidney, and moderate levels were found in the lung, blood, dental pulp and the walls of the stomach. Radioactivity was the lowest in the skeletal muscle, testis, eye and brain. After reaching peak levels, radioactivity in the body decreased gradually, and it was detected only in the excretory organs at 24 h after drug administration. The distribution pattern after the intravenous dose was essentially similar to that after oral administration. The distribution profile of radioactivity in non-pregnant female rats after an oral dose was similar to that in male rats. Placental transfer and excretion in milk of radioactivity was slight. When the affinity of this compound to the melanin-containing tissues such as the uveal tract of the eye and the hair follicle was examined using pigmented rats, no tendency to retention of radioactivity in these tissues was observed.
Naito
K
K
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Nakahara
M
M
Yamada
Y
Y
Otsuka
M
M
Takaiti
O
O
Harigaya
S
S
Parnes
H
H
Chaplin
M
M
D000284:Administration, Oral; D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D001345:Autoradiography; D016620:Enprostil; D005260:Female; D007275:Injections, Intravenous; D007774:Lactation; D008297:Male; D011247:Pregnancy; D011459:Prostaglandins E, Synthetic / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; D016620:Enprostil