Human bioequivalence evaluation of two losartan potassium tablets under fasting conditions

A K Das, S Dhanure, A K Savalia, S K Nayak, S K Tripathy, A K Das, S Dhanure, A K Savalia, S K Nayak, S K Tripathy

Abstract

The bioequivalence of two different tablet formulations containing losartan potassium 100 mg was determined in healthy volunteers after a single oral dose in a randomized crossover study. Test and reference products were administered to 60 volunteers with 240 ml water after overnight fasting. Plasma concentrations of losartan and its active carboxylic acid metabolite were monitored over a period of 36 h after drug administration by validated LC/MS/MS analytical method. The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞, AUC0-t/AUC0-∞, tmax, Kel and t½ were determined from plasma concentration time profile of both formulations for losartan and its active metabolite losartan carboxylic acid and were found to be in good agreement. The carboxylic acid metabolite was considered for profiling purpose only. The analysis of variance did not show any significant difference between the two formulations and 90% confidence intervals for the ratio of Cmax (84.89-104.09%), AUC0-t (95.84-102.84%) and AUC0-∞ (96.43-103.25%) values for losartan between the test and reference products were within the 80-125% interval, satisfying the bioequivalence criteria of the US FDA guidelines. These results indicate that the test and the reference products of losartan potassium are bioequivalent and, thus, may be prescribed interchangeably.

Keywords: ANOVA; Losartan Potassium; angiotensin; bioequivalence; hypertension.

Figures

Fig. 1
Fig. 1
Structure of losartan potassium.
Fig. 2
Fig. 2
Mean plasma concentration-time profile (untransformed) of losartan. Test, Reference.
Fig. 3
Fig. 3
Mean plasma concentration-time profile (log-transformed) of losartan. Test, Reference.
Fig. 4
Fig. 4
Mean plasma concentration-time profile (untransformed) of losartan carboxylic acid. Test, Reference.
Fig. 5
Fig. 5
Mean plasma concentration-time profile (log-transformed) of losartan carboxylic acid. Test, Reference.

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Source: PubMed

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