Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers
| Autor: | G De Meyer, R Verbesselt, G Somers, M De Smet, V Fitzpatrick, D F Schoors, Michael R. Goldberg |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Digoxin Cardiotonic Agents Administration Oral Tetrazoles Angiotensin II receptor antagonist Pharmacology Placebo Losartan Pharmacokinetics Double-Blind Method Oral administration medicine Humans Pharmacology (medical) Antihypertensive Agents Cross-Over Studies business.industry Biphenyl Compounds Imidazoles Angiotensin II Biphenyl compound Injections Intravenous business medicine.drug circulatory and respiratory physiology Research Article |
| Zdroj: | British journal of clinical pharmacology. 40(6) |
| ISSN: | 0306-5251 |
| Popis: | 1 Losartan (DuP 753, MK-954) is a novel, potent and highly selective AT(1) angiotensin 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 daily) did not affect the pharmacokinetic parameters of 0.5 mg of digoxin i.v. AUC(0,48h) of immunoreactive digoxin during losartan 28.8 +/- 2.9 vs 28.5 +/- 3.9 ng ml(-1) h during placebo; not significant, and 96 h urinary excretion [% dose] during losartan 54.0 +/- 7.2 us 51.9 +/- 6.5% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.03 (0.98, 1.08) and 1.09 (0.98, 1.21). 5 Multiple oral doses of losartan did not affect the pharmacokinetic parameters of oral digoxin AUC(0,48h) during losartan 23.6 +/- 3.7 ng ml(-1) h vs 22.4 +/- 2.6 ng ml(-1) h during placebo; not significant, C-max 3.5 +/- 0.7 ng ml(-1) with us 3.1 +/- 0.5 ng ml(-1) without losartan; not significant and t(max) 0.6 +/- 0.2 h with vs 0.9 +/- 0.7 h without losartan; not significant, and 96 h urinary excretion [% dose] during losartan 51.2 +/- 6.3 vs 46.3 +/- 2.4% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.06 (0.98, 1.14) and 1.12 (0.97, 1.28). 6 We conclude that multiple oral doses of losartan (50 mg daily) do not alter the pharmacokinetics of immunoreactive digoxin, following either intravenous or oral digoxin. Furthermore, the co-administration of digoxin with losartan is well tolerated by healthy male volunteers. |
| Databáze: | OpenAIRE |
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