Pharmacokinetics of Eprosartan in Healthy Subjects, Patients with Hypertension, and Special Populations

Abstract

After oral administration of eprosartan to healthy volunteers, bioavailability is approximately 13%, with peak plasma concentrations occurring 1-2 hours after an oral dose in the fasted state. Food slows the rate of absorption and changes the overall extent by less than 25%, which is unlikely to be of clinical consequence. Plasma concentrations increase in a slightly less than dose-proportional manner from 100-800 mg. There is no evidence of significant accumulation of eprosartan with long-term therapy. The drug's terminal elimination half-life is typically 5-9 hours after oral administration. The agent is highly protein bound (approximately 98%), with low plasma clearance (approximately 130 ml/minute) and small volume of distribution (approximately 13 L). It is primarily unmetabolized by the liver, with less than 2% of an oral dose recovered in the urine as a glucuronide. Biliary (primary) and renal excretion contribute to its elimination. No dosage adjustment is required in patients with mild to moderate renal impairment. Although an increase in systemic exposure to eprosartan was observed in the elderly, in patients with hepatic impairment, and in those with severe renal disease, this finding is unlikely to be of clinical consequence, based on the drug's excellent safety and tolerability profile (doses up to 1200 mg) in phase III clinical trials in hypertensive patients. Eprosartan can be safely administered to these special populations without an initial dosage adjustment, with subsequent dosing individualized based on tolerability and response.

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension

“…119,149 Hypertension has no effect on the pharmacokinetics of eprosartan. 119 In subjects with severe renal impairment, higher C max (by 35%) and AUC (by 55%) are found, and a decrease in Cl T by 95%, 119,120 however, dosage adjustment is not necessary in patients with renal impairment. 119,120 Hepatic disease causes an increase in AUC (40%), 123 and it is recommended to individualise the dose of eprosartan, based on tolerability and response, in patients with liver disease.…”

“…14,15 Eprosartan: After oral administration, eprosartan is fairly rapidly absorbed (T max = 1-3 h), but its bioavailability (Table 6a) is low (about 13%) due to incomplete absorption. 11,118,119 High fat food increases bioavailability [increase in peak plasma levels (C max ) by 80% and in the area under the plasma level-time curve (AUC) by 55%], but slows its absorption, possibly by prolonging residence time in the gastrointestinal tract; 11,118,120,121 these changes do not require dosage adjustment in the fasting state. 11 The dose-C max and dose-AUC relationships for single doses in the range of 100-800 mg of eprosartan, are less than proportional due to saturation of absorption.…”

“…of orally administered eprosartan is 5-9 h (about 2 h after intravenous administration). 11,[118][119][120] The drug does not accumulate after repeated dosing. 124 Eprosartan is metabolised to a small extent, by enzymes other than cytochrome P450.…”

“…14,15,117 The elderly have about two-fold higher C max and AUC (for both total and unbound eprosartan in plasma) compared to young (most likely due to increased bioavailability of the drug in the elderly); 149 the T max is also higher (by 2.5 h) in the elderly. 119,149 However, no initial dosage adjustment is necessary in the elderly. 119,149 Hypertension has no effect on the pharmacokinetics of eprosartan.…”

“…119,149 However, no initial dosage adjustment is necessary in the elderly. 119,149 Hypertension has no effect on the pharmacokinetics of eprosartan. 119 In subjects with severe renal impairment, higher C max (by 35%) and AUC (by 55%) are found, and a decrease in Cl T by 95%, 119,120 however, dosage adjustment is not necessary in patients with renal impairment.…”