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Absorption, distribution and protein binding of 14C-telmisartan (BIBR 277 SE) were investigated in rats after a single oral administration. 1. After oral administration of 14C-telmisartan (1 mg/kg) to fasted rats, the radioactivity was absorbed rapidly in both male and female rats, and the maximum plasma level (Cmax) of 184.79-250.55 ng eq./ml was reached within 1 hr. Elimination half-lives (t1/2 (8-24hr)) in male and female rats were about 7 hr. The plasma level-time profiles in males and females were similar. 2. The effect of food intake on the drug absorption in male rats was investigated. The Cmax and AUC(0-48hr) were about 37% and 77% of those of fasted rats, respectively. The absorbed amount of 14C-telmisartan after oral administration was thus slightly decreased by food intake. 3. The ligated loop method was used to examine the absorption sites. Absorption ratios in the stomach at 30, 60 and 120 min after administration were 12.5, 28.3 and 24.2%, respectively. Those in the duodenum, the jejunum, the ileum and the colon at 30, 60 and 120 min after administration were 43.1-61.9, 43.9-78.5 and 79.4-86.3%, respectively. These findings suggested that 14C-telmisartan is readily absorbed throughout the gastrointestinal tract, except the stomach. 4. Radioactivity in tissues after oral administration of 14C-telmisartan (1 mg/kg) to fasted male rats was investigated. Radioactivity in most tissues peaked at 0.5 hr after administration. High levels of radioactivity were observed in the liver and gastrointestinal tract, including its content. The central nervous system showed only a low radioactivity content. The levels of radioactivity in tissues rapidly decreased with time. Thus, there was no marked accumulation of radioactivity in any tissue. 5. Distribution of radioactivity into blood cells was low at all sampling points after administration. The in vivo plasma protein binding of radioactivity was very high, being greater than 99% at 30 min after administration.

Pharmacokinetics of 14C-Telmisartan. (1). Absorption, Distribution and Protein Binding of 14C-Telmisartan after a Single Oral Administration to Rats.