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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

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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.


Mean (A) SBP, (B) DBP, and (C) PR after a single oral administration 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: SBP, systolic blood pressure; h, hours; DBP, diastolic blood pressure; PR, pulse rate.
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f3-dddt-10-3021: Mean (A) SBP, (B) DBP, and (C) PR after a single oral administration 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: SBP, systolic blood pressure; h, hours; DBP, diastolic blood pressure; PR, pulse rate.

Mentions: As shown in Figure 3A–C, similar reductions in the 24-hour SBP, DBP, and mean PR were observed for the test drug and reference drug. The mean SBP and DBP were lower than the baseline values at 6–8 hours after dosing (Figure 3A–C). The mean PR showed a tendency to increase 6 hours after dosing. The lowest mean values (standard deviation) for SBP were 102.2 mmHg (9.4 mmHg) and 100.1 mmHg (8.8 mmHg), which were measured at 8 hours after administration of the test and reference drugs, respectively. The lowest mean values (standard deviation) for DBP were 57.0 mmHg (6.2 mmHg), measured 6 hours after the administration of the test drug, and 57.2 mmHg (6.2 mmHg), measured 8 hours after the administration of the reference drug. No clinically significant symptoms related to BP reduction were observed in our study.


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
Mean (A) SBP, (B) DBP, and (C) PR after a single oral administration 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: SBP, systolic blood pressure; h, hours; DBP, diastolic blood pressure; PR, pulse rate.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dddt-10-3021: Mean (A) SBP, (B) DBP, and (C) PR after a single oral administration 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: SBP, systolic blood pressure; h, hours; DBP, diastolic blood pressure; PR, pulse rate.
Mentions: As shown in Figure 3A–C, similar reductions in the 24-hour SBP, DBP, and mean PR were observed for the test drug and reference drug. The mean SBP and DBP were lower than the baseline values at 6–8 hours after dosing (Figure 3A–C). The mean PR showed a tendency to increase 6 hours after dosing. The lowest mean values (standard deviation) for SBP were 102.2 mmHg (9.4 mmHg) and 100.1 mmHg (8.8 mmHg), which were measured at 8 hours after administration of the test and reference drugs, respectively. The lowest mean values (standard deviation) for DBP were 57.0 mmHg (6.2 mmHg), measured 6 hours after the administration of the test drug, and 57.2 mmHg (6.2 mmHg), measured 8 hours after the administration of the reference drug. No clinically significant symptoms related to BP reduction were observed in our 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.