Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans

Clinical Pharmacology and Therapeutics

Volumn 58, Issue 6, 1995, Pages 641-649

  Lo, Man Wai ^a   Goldberg, Michael R ^b   McCrea, Jacqueline B ^b   Lu, Hannah ^b   Furtek, Christine I ^b   Bjornsson, Thorir D ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

2 BUTYL 4 CHLORO 1 [[2' (1H TETRAZOL 5 YL) 4 BIPHENYLYL]METHYL] 5 IMIDAZOLECARBOXYLIC ACID; ANGIOTENSIN II ANTAGONIST; DRUG METABOLITE; LOSARTAN;

ADULT; AREA UNDER THE CURVE; ARTICLE; BIOAVAILABILITY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG STRUCTURE; HUMAN; HUMAN EXPERIMENT; INTRAVENOUS DRUG ADMINISTRATION; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHARMACOKINETICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

EID: 0029588499     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1016/0009-9236(95)90020-9     Document Type: Article

References (22)

1. Dzau VJ, Pratt RE. Renin-angiotensin system: biology, physiology and pharmacology. In: Fozzard HA, Haber E, Jennings RB, Katz AM, Morgan HE, eds. The heart and cardiovascular system; vol 2. New York: Raven Press, 1986:1631-62.
2. Brogden RN, Todd PA, Sorkin EM. Captopril: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs 1988;36:540-600.
3. Borek M, Charlap S, Frishman W. Enalapril: a long-acting angiotensin-converting enzyme inhibitor. Pharmacotherapy 1987;7:133-48.
4. Inagaki T, Ohtsuki K, Inagami T. Mouse submaxillary renin has a protease activity and converts human plasma inactive prorenin to an active form. J Biol Chem 1983;258:7476-80.
5. Andersson RGG, Persson K. ACE inhibitors and their influence on inflammation, bronchial reactivity and cough. Eur Heart J 1994;15(suppl C):52-6.
6. Wong PC, Barnes TB, Chiu AT, et al. Losartan (DuP 753), an orally active nonpeptide angiotensin II receptor antagonist. Cardiovasc Drug Rev 1991;9:317-39.
7. Gradman AH, Arcuri KE, Goldberg AI, et al. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension 1995;25:1345-50.
8. Tsunoda K, Abe K, Hagino T, et al. Hypotensive effect of losartan, a nonpeptide angiotensin II receptor antagonist, in essential hypertension. Am J Hypertens 1993;6:28-32.
9. Weber MA, Byyny RL, Pratt H, et al. Blood pressure effects of the angiotensin II receptor blocker, losartan. Arch Intern Med 1995;155:405-11.
10. Goldberg AI, Dunlay MC, Sweet CS. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide. atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. Am J Cardiol 1995;75:793-5.
11. Wong PC, Price WA, Chiu AT, et al. Nonpeptide angiotensin II receptor antagonists; XI: pharmacology of EXP3174, an active metabolite of DuP 753 - an orally active antihypertensive agent. J Pharmacol Exp Ther 1990;255:211-7.
12. Munafo A, Christen Y, Nussberger J, et al. Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist. CLIN PHARMACOL THER 1992;51:513-21.
13. Stearns RA, Chakravarty PK, Chen R, Chiu SHL. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Drug Metab Dispos 1995;23:207-15.
14. Shum L, Benedek IH, Quon CY, Robinson CA, Borland RM. Pharmacokinetics of DuP 753 (MK 954) in healthy male volunteers after single oral ascending doses [Abstract]. Pharm Res 1991;8:S310.
15. Ohtawa M, Takayama F, Saitoh K, Yoshinaga T, Nakashima M. Pharmacokinetics and biochemical efficacy after single and multiple oral administration of losartan, an orally active nonpeptide angiotensin II receptor antagonist, in humans. Br J Clin Pharmacol 1993;35:290-7.
16. Furtek CI, Lo MW. Simultaneous determination of a novel angiotensin II receptor blocking agent, losartan, and its metabolite in human plasma and urine by high-performance liquid chromatography. J Chromatogr Biomed Appl 1992;573:295-301.
17. Lam FC, HungCR, PerrierDG. Estimation of variance for harmonic mean half-lives. J Pharm Sci 1985;74:229-31.
18. Perrier D, Mayersohn M. Noncompartmental determination of the steady-state volume of distribution for any mode of administration. J Pharm Sci 1982;71:372-3.
19. Pang KS, Kwan KC. A Commentary: methods and assumptions in the kinetic estimation of metabolite formation. Drug Metab Dispos 1983;11:79-84.
20. Christ DD. Human plasma protein binding of the angiotensin II receptor antagonist losartan potassium (DuP-753/MK 954) and its pharmacologically active metabolite EXP3174. J Clin Pharmacol 1995;35:515-20.
21. Sica DA, Lo MW, Shaw WC, et al. Pharmacokinetics of losartan in renal insufficiency. J Hypertens 1995;13(suppl 1):S49-52.
22. Gibaldi M. Biopharmaceutics and clinical pharmacokinetics. 4th ed. Philadelphia: Lea & Febiger, 1991:154-6.