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Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

View Article: PubMed Central - PubMed

ABSTRACT

Background: A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects.

Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once.

Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated.

Conclusion: An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male subjects.

No MeSH data available.


Individual comparisons of the (A) Cmax of amlodipine, (B) the AUC0–t of amlodipine, (C) the Cmax of losartan, and (D) the AUC0–t of losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).Abbreviations: h, hours; Cmax, maximum plasma concentration; AUC0–t, area under the concentration curve from time zero to the last quantifiable time point.
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f2-dddt-10-3021: Individual comparisons of the (A) Cmax of amlodipine, (B) the AUC0–t of amlodipine, (C) the Cmax of losartan, and (D) the AUC0–t of losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).Abbreviations: h, hours; Cmax, maximum plasma concentration; AUC0–t, area under the concentration curve from time zero to the last quantifiable time point.

Mentions: The plasma concentration–time profiles of amlodipine and losartan were similar for both FDCs (Figure 1A and B). The Cmax values of amlodipine and losartan in both FDCs were reached at ~6 hours and 1 hour, respectively, after dosing. The terminal elimination t1/2 values for amlodipine and losartan in both FDCs were 43.6–46.4 hours and 1.8–1.9 hours, respectively. The individual differences in the Cmax and AUC0–t values of amlodipine and losartan showed no obvious trends between the two treatments (Figure 2A–D). The PK parameters of amlodipine and losartan for the test and reference treatments are presented in Table 1. Both drugs had similar PK properties for each component.


Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study
Individual comparisons of the (A) Cmax of amlodipine, (B) the AUC0–t of amlodipine, (C) the Cmax of losartan, and (D) the AUC0–t of losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).Abbreviations: h, hours; Cmax, maximum plasma concentration; AUC0–t, area under the concentration curve from time zero to the last quantifiable time point.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036556&req=5

f2-dddt-10-3021: Individual comparisons of the (A) Cmax of amlodipine, (B) the AUC0–t of amlodipine, (C) the Cmax of losartan, and (D) the AUC0–t of losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).Abbreviations: h, hours; Cmax, maximum plasma concentration; AUC0–t, area under the concentration curve from time zero to the last quantifiable time point.
Mentions: The plasma concentration–time profiles of amlodipine and losartan were similar for both FDCs (Figure 1A and B). The Cmax values of amlodipine and losartan in both FDCs were reached at ~6 hours and 1 hour, respectively, after dosing. The terminal elimination t1/2 values for amlodipine and losartan in both FDCs were 43.6–46.4 hours and 1.8–1.9 hours, respectively. The individual differences in the Cmax and AUC0–t values of amlodipine and losartan showed no obvious trends between the two treatments (Figure 2A–D). The PK parameters of amlodipine and losartan for the test and reference treatments are presented in Table 1. Both drugs had similar PK properties for each component.

View Article: PubMed Central - PubMed

ABSTRACT

Background: A fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects.

Subjects and methods: A randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography–tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0–t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once.

Results: The PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0–t were 0.98 (0.94−1.01) and 0.97 (0.93−1.01), respectively. The corresponding values for losartan were 0.91 (0.81−1.02) and 1.05 (0.98−1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated.

Conclusion: An FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0–t values. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male subjects.

No MeSH data available.