生物等效性和生物利用度杂志

抽象的

Pharmacokinetic Evaluation of Administration of Losartan with Aspirin in Healthy Volunteers

Mendes GD, Ferreira PMF, Gagliano-Jucá T, Magalhães JCDA, Santos EM, Sampaio M and De Nucci G

Losartan and aspirin are often used concomitantly in patients with heart failure, ischemic heart disease and hypertension. Objectives: To investigate whether aspirin co-administration affects losartan bioavailability. Methods: 1) Twenty-four healthy volunteers from both sexes were recruited. Volunteers received a single 50 mg losartan with or without a 81 mg aspirin tablet. Blood samples were obtained at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12 hour post-dosing. The concentrations of losartan were analyzed by LC-MSMS. Clearance (Cl) and T1/2 were used to evaluate a possible drug-drug interaction. Cmax and AUC0-8 were used to evaluate whether co-administration interferes on the bioavailability process. Results: From the losartan plasma concentrations vs. time curves the following pharmacokinetic parameters were obtained: ASC0-8 hours, AUCinf, Cmax, Cl, Vd, Tmax, Ke and T1/2. No significant differences were observed in T1/2 (p-value = 0.431), Cl (p-value = 0.554), AUC0-8 hours (p-value = 0.590), Cmax (p-value = 0.987) and Vd (p-value = 0.647). Conclusions: Since there is no significant difference in losartan bioavailability and elimination when coadministered with aspirin, we conclude that there is no pharmacokinetic interaction between both drugs. The finding is important since it reassures the safe use of combining AAS to losartan treatment.