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Author: Admin | 2025-04-28
Losartan, about 45% of radioactivity is recovered in the urine and 50% in the feces. Neither losartan nor its metabolite accumulates inplasma upon repeated once-daily dosing.Specific PopulationsPediatricPharmacokinetic parameters after multiple doses of losartan (average dose 0.7 mg/kg, range 0.36 to 0.97 mg/kg) as a tablet to 25 hypertensive patients aged 6to 16 years are shown in Table 4 below. Pharmacokinetics of losartan and its active metabolite were generally similar across the studied age groups and similar tohistorical pharmacokinetic data in adults. The principal pharmacokinetic parameters in adults and children are shown in the table below.Table 2: Pharmacokinetic Parameters in Hypertensive Adults and Children Age 6-16 Following Multiple Dosing Adults given 50 mg once daily for 7 days N=12 Age 6-16 given 0.7 mg/kg once daily for 7 days N=25 Parent Active Metabolite Parent Active Metabolite AUC0-24 (ng·hr/mL)* 442 ± 173 1685 ± 452 368 ± 169 1866 ± 1076 CMAX (ng/mL)* 224 ± 82 212 ± 73 141 ± 88 222 ± 127 T1/2 (h)† 2.1 ± 0.70 7.4 ± 2.4 2.3 ± 0.8 5.6 ± 1.2 TPEAK (h)‡ 0.9 3.5 2.0 4.1 CLREN (mL/min)* 56 ± 23 20 ± 3 53 ± 33 17 ± 8 * Mean ± standard deviation † Harmonic mean and standard deviation ‡ Median The bioavailability of the suspension formulation was compared with losartan tablets in healthy adults. The suspension and tablet are similar in their bioavailability withrespect to both losartan and the active metabolite [see DOSAGE AND ADMINISTRATION] .Geriatric And GenderLosartan pharmacokinetics have been investigated in the elderly (65-75 years) and in both genders. Plasma concentrations of losartan and itsactive metabolite are similar in elderly and young hypertensives. Plasma concentrations of losartan were about twice as high in female hypertensives as malehypertensives, but concentrations of the active metabolite were similar in males and females. No dosage adjustment is necessary [see DOSAGE AND ADMINISTRATION] .RacePharmacokinetic differences due to race have not been studied [see Use In Specific Populations] .Renal InsufficiencyFollowing oral administration, plasma concentrations and AUCs of losartan and its active metabolite are increased by 50-90% in patients with mild(creatinine clearance of 50 to 74 mL/min) or moderate (creatinine clearance 30 to 49 mL/min) renal insufficiency. In this study, renal clearance was reduced by 55-85%for both losartan and its active metabolite in patients with mild or moderate renal insufficiency. Neither losartan nor its active metabolite can be removed byhemodialysis [see WARNINGS AND PRECAUTIONS and Use In Specific Populations] .Hepatic InsufficiencyFollowing oral administration in patients with mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of losartan and its activemetabolite were, respectively, 5-times and about 1.7-times those in young male volunteers. Compared to normal subjects the total plasma clearance of losartan inpatients with hepatic insufficiency was about 50% lower and the oral bioavailability was about doubled. Use a starting dose of 25 mg for patients with mild to moderatehepatic impairment. COZAAR has not been studied in patients with severe hepatic impairment [see DOSAGE AND ADMINISTRATION and Use In Specific Populations] .Drug InteractionsNo clinically significant
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