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Updated: Jan 27, 2026

Sampling and Pretreatment of Tooth Enamel Carbonate for Stable Carbon and Oxygen Isotope Analysis
Published on: August 15, 2018
Analysis of the Complicated Nonlinear Pharmacokinetics of Orally Administered Telmisartan in Rats Using a Stable
Keiko Minami1, Haruki Higashino1, Makoto Kataoka1
1Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Abstract:
This study aimed to kinetically analyze the nonlinear absorption and systemic exposure of telmisartan (TEL) after oral administration to rats by using a stable isotope-IV method. Rats were orally administered different dose of TEL, followed by the intravenous injection of 0.005 mg/kg of deuterium-labeled TEL (TEL-d3). Assuming that TEL-d3 shows same pharmacokinetic properties with TEL, systemic clearance (CLtot), oral bioavailability (Foral), and intestinal and hepatic availability (Fa*Fg, Fh) of TEL were calculated in each individual rat. AUCpo of TEL increased disproportionately with dose and showed a sigmoid-type relation, indicating the involvement of multi-nonlinear processes in oral absorption of TEL. Fa*Fg of TEL increased with dose at the low-dose range while decreased at the high-dose range. In contrast, Fh increased and CLtot decreased significantly in the middle range (2 to 6 mg/kg). As main factors of nonlinearity, saturations of solubility, efflux transport in the intestine, and the hepatic uptake of TEL were indicated. In conclusion, this study demonstrated a high possibility of a stable isotope-IV method to characterize complicated pharmacokinetic properties of oral drugs in animals, which can help to consider the future risks in their clinical use.
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