Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.

Abstract

1 Losartan (DuP 753, MK-954) is a novel, potent and highly selective AT1angiotensin II receptor antagonist. The effect of multiple oral doses of losartan on digoxin pharmacokinetics was evaluated in healthy male subjects. 2 In a double-blind and randomized fashion, subjects received 50 mg losartan or placebo once daily for 15 days in each period. At least 7 days elapsed between the two treatment periods. On days 4 and 11 of each period, subjects also received a single 0.5 mg dose of digoxin intravenously and orally respectively. 3 Eleven of 13 subjects completed the study. Side effects were mild and transient (12 out of 13 subjects reported at least one adverse experience). During the study, no laboratory abnormalities were noted. 4 Multiple oral doses of losartan (50 mg

Interaction of angiotensin II type 1 receptor blockers with P-gp substrates in Caco-2 cells and hMDR1-expressing membranes

“…In our results, the [I]/IC 50 values of candesartan cilexetil, irbesartan and losartan, which did not cause any adverse events in a clinical DDI study (De Smet et al 1995;Marino and Vachharajani 2001;Jonkman et al 1997), were calculated to be less than 50. In particular, that of candesartan cilexetil and losartan was less than 10.…”

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

“…Losartan does not alter the pharmacokinetics of digoxin 163 or pharmacokinetics and pharmacodyn-S81 amics of warfarin, 164 hence, no dosage adjustment of digoxin or warfarin are needed. There is no clinically significant pharmacokinetic interaction between losartan and hydrochlorothiazide in hypertensive patients.…”

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…On the basis of such data, losartan conversion to EXP3174 has also been used as a probe to study potential inhibition of CYP2C9 by other compounds, e.g., the antimalaria drug amodiaquine (Wennerholm et al, 2006). Losartan did not affect the pharmacokinetics or pharmacodynamics of a single dose of warfarin (Kong et al, 1995) or the pharmacokinetics of oral or intravenous digoxin (De Smet et al, 1995). There also is no pharmacokinetic interaction between losartan and hydrochlorothiazide.…”