The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction

Orally administered olmesartan medoxomil was rapidly absorbed from the gastrointestinal tract and converted during absorption to olmesartan, the pharmacologically active metabolite that was subsequently excreted without further metabolism. The medoxomil moiety was released as diacetyl that was rapidly cleared by further metabolism and excretion. Peak plasma concentrations of olmesartan occurred 1–3 h after administration, after which concentrations decreased quickly. The elimination half-life was 10–15 h. Olmesartan medoxomil was not measurable in plasma and excreta. The volume of distribution was low, consistent with limited extravascular tissue distribution. Bioavailability (Cmax and area under the curve) increased approximately in proportion with dose, after single and multiple daily oral doses, over the therapeutic dose range (up to 40–80 mg daily), above which systemic availability of olmesartan increased less than proportionally with increase in dose. Steady-state plasma concentrations of olmesartan were reached within the first few daily oral doses. On average, approximately 40% of systemically available olmesartan was excreted by the kidneys, the remainder being excreted in faeces, following secretion in bile. Renal clearance (0.5–0.7 l/h) was independent of dose, accounting for approximately 9–12% of an oral dose. The absolute bioavailability of olmesartan from olmesartan medoxomil tablets was 28.6%. Olmesartan exhibited little or no binding to blood cells. No clinically significant steady-state pharmacokinetic interactions were observed following co-administration of olmesartan medoxomil with digoxin, warfarin and aluminium magnesium hydroxide (antacid), supporting the low potential for clinically significant pharmacokinetic interactions to occur between olmesartan medoxomil and co-administered drugs.J Hypertens19 (suppl 1):S21-S32 © 2001 Lippincott Williams & Wilkins.