Absorption, Metabolism, and Excretion of Intravenously and Orally Administered [14C]Telmisartan in Healthy Volunteers

• Published in: Journal of clinical pharmacology Vol. 40; no. 12; pp. 1312 - 1322
• Main Authors: Stangier, Joachim, Schmid, Jochen, Türck, Dietrich, Switek, Heinz, Verhagen, Aalt, Peeters, Pierre A. M., van Marle, Sjoerd P., Tamminga, Wim J., Sollie, Frans A. E., Jonkman, Jan H. G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2000; SAGE Publications
• Subjects: Absorption; Administration, Oral; Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - blood; Angiotensin-Converting Enzyme Inhibitors - chemistry; Angiotensin-Converting Enzyme Inhibitors - pharmacokinetics; Angiotensin-Converting Enzyme Inhibitors - urine; Benzimidazoles - adverse effects; Benzimidazoles - blood; Benzimidazoles - chemistry; Benzimidazoles - pharmacokinetics; Benzimidazoles - urine; Benzoates - adverse effects; Benzoates - blood; Benzoates - chemistry; Benzoates - pharmacokinetics; Benzoates - urine; Carbon Radioisotopes; Humans; Infusions, Intravenous; Male; Middle Aged; Structure-Activity Relationship
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/009127000004001202

The study was conducted in healthy male volunteers to evaluate the absorption, metabolic pattern, and mode of elimination of telmisartan, a nonpeptide angiotensin II receptor antagonist. [14C]telmisartan was administered orally in solution as a single 40 mg dose to 5 subjects. A further 5 subjects received short‐term intravenous infusion of [14C]telmisartan 40 mg. Measurement of total 14C radioactivity in plasma showed that about 50% was absorbed following oral administration, with maximum plasma concentration observed after 0.5 to 1 hour. Absolute bioavailability was 43%. On average, 84% of total radioactivity in plasma reflected the parent compound. The remainder of total radioactivity could be ascribed to the glucuronide conjugate of telmisartan, which represented the only metabolite in man. About 99.5% of telmisartan was bound to plasma protein, mainly to albumin and α‐1‐acid glycoprotein. Telmisartan was reversibly distributed into erythrocytes. More than 90% of administered dose was excreted within 120 hours, and the excretion balance was complete 144 hours after dosing. Radioactivity was almost exclusively (> 98%) excreted via the feces; urinary excretion accounted for < 1% of the dose, irrespective of the route of administration. In the small fraction excreted into urine, the glucuronide conjugate of telmisartan was predominant. Although some telmisartan glucuronide was detected in plasma, only unchanged drug was identified in the feces. No changes in vital signs, electrocardiogram, or clinical laboratory tests were detected following telmisartan administration, and adverse events, predominantly unrelated to treatment and of mild intensity, were infrequent. One subject fainted and, on another occasion, reported faintness; these events were probably due to the antihypertensive action of the intravenous study medication.