Metabolic fate of the new anti-ulcer drug enprostil in animals. 3rd communication: tissue accumulation after consecutive oral administration of [3H]-enprostil in rats.
Accumulation characteristics of radioactivity in organs and tissues were investigated after oral 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) to male rats once a day (20 micrograms/kg/d) for 1, 7 or 14 days. [3H]-Enprostil was found to be partially metabolized in vivo to volatile tritium (3H2O). The ratios of volatile tritium to total radioactivity in plasma increased with repeated administration of [3H]-enprostil and the levels of volatile tritium were almost equilibrated within 7 days of drug administration. The formation rate of volatile tritium was estimated to be 1-2% of the single dose. The blood levels of non-volatile radioactivity at 1 h after each daily dosing were nearly constant. The levels at 24 h, however, increased with repeated dosing. The levels of non-volatile radioactivity in most tissues at 1 h after the multiple administration (7 and 14 times) were higher than those after the single dose. At 24 h, levels were noticeable after multiple dosing even in the tissues in which levels below the detection limit were found after the single dose. From the comparison of the multiple-dose groups, the levels in most tissues attained steady state within 7 times dosing. The daily excretions of radioactivity in the urine, feces and expired air were constant throughout the period of consecutive administration. The total recovery of administered dose was 92%, which was similar to that achieved in the single-dosing group. As described above, the retention of non-volatile radioactivity was observed in most tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Kohno
M
M
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Naito
K
K
Yamada
Y
Y
Nakahara
M
M
Otsuka
M
M
Takaiti
O
O
Parnes
H
H
Chaplin
M
M
D000284:Administration, Oral; D000388:Air / Q000032:analysis; D000818:Animals; D000897:Anti-Ulcer Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D016620:Enprostil; D005243:Feces / Q000032:analysis; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; D016620:Enprostil