What question did this study set out to answer?

To investigate the potential influence of repeated doses of the oral direct renin inhibitor aliskiren on the pharmacokinetic and pharmacodynamic profiles of a single dose of warfarin.

June 16, 2004British Journal of Clinical PharmacologyOpen Access

Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects

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Why the study?

Does aliskiren affect the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects?

Population

15 healthy male and female subjects

Comparison

Aliskiren 150 mg daily for 8 days with a single… vs Placebo daily for 8 days with a single oral dose…

Design

RCT, randomized, two-period crossover, single-blind, placebo-controlled

Authors

WDW. DieterlePIQUR Therapeutics (Switzerland)SCSophie Corynen JMJessica MannMassachusetts General Hospital

Discussion

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Implication

Aliskiren may be co-administered with warfarin without dose adjustment; confirms absence of interaction in RCT.

Key Points

To investigate the potential influence of repeated doses of the oral direct renin inhibitor aliskiren on the pharmacokinetic and pharmacodynamic profiles of a single dose of warfarin.
Conducted a single-blind, placebo-controlled, randomized, two-period crossover trial in 15 healthy male and female subjects.
Administered a single oral dose of 25 mg racemic warfarin on the eighth day of once-daily treatment with either 150 mg aliskiren or placebo.
Monitored blood coagulation markers (prothrombin time, INR, activated partial thromboplastin time) and measured plasma concentrations of (R)- and (S)-warfarin over time.
Aliskiren treatment produced no measurable effect on blood coagulation parameters, with unchanged prothrombin time, INR, and activated partial thromboplastin time.
Least squares mean ratios (90% CI) for aliskiren versus placebo demonstrated identical total exposure, with AUC(0, infinity) of 1.00 (0.94, 1.07) for (R)-warfarin and 1.06 (0.96, 1.16) for (S)-warfarin.
Peak plasma concentration ratios (90% CI) were 0.89 (0.82, 0.96) for (R)-warfarin and 0.88 (0.80, 0.97) for (S)-warfarin, while elimination half-lives remained unchanged at 0.99 (0.92, 1.07) and 1.05 (0.96, 1.14).

Structured PICO

Does aliskiren affect the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects?

Population

15 healthy male and female subjects

Intervention

Aliskiren 150 mg daily for 8 days with a single oral dose of 25 mg racemic warfarin on the 8th day

Comparator

Placebo daily for 8 days with a single oral dose of 25 mg racemic warfarin on the 8th day

Outcome

Pharmacokinetics (plasma concentrations of (R)- and (S)-warfarin) and pharmacodynamics (prothrombin time, INR, and activated thromboplastin time)surrogate

Multiple doses of aliskiren do not alter the pharmacokinetics or pharmacodynamics of a single dose of warfarin, suggesting no clinically significant drug-drug interaction.

Cite This Study

Dieterle et al. (2004) studied this question.

synapsesocial.com/papers/6a1d7f751024216094057233 https://doi.org/10.1111/j.1365-2125.2004.02160.x

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Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Effect of the oral renin inhibitor aliskiren on the pharmacokinetics and pharmacodynamics of a single dose of warfarin in healthy subjects

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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