How well have animal studies with losartan predicted responses in humans?
OBJECTIVE
To compare the biological activity of losartan as seen in several animal studies with results from similar clinical studies in hypertensive patients or normal volunteers.


RESULTS
With regard to oral bioavailability and estimates of oral angiotensin II blocking activity, the animal models were reasonably good predictors of the human response. Although formation of the major losartan metabolite E 3174 differs according to species, both animal and human studies suggest an association between plasma drug levels and angiotensin II blockade. The finding that losartan demonstrated increased sensitivity during salt depletion in animals was confirmed in humans. Possible beneficial effects on renal function await further detailed clinical trials.


CONCLUSIONS
Losartan has been shown to lower blood pressure in patients with essential hypertension. However, cross-species comparisons are difficult because, unlike humans, animal models of hypertension follow clearly defined hypertensive mechanisms. Differing profiles of E 3174 metabolite formation also make cross-species comparisons difficult.
Sweet
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Merck Research Laboratories, West Point, Pennsylvania 19486.
Nelson
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D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D019808:Losartan; D012964:Sodium / Q000172:deficiency; D013777:Tetrazoles / Q000493:pharmacokinetics / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D012964:Sodium; D019808:Losartan