Dataset Information

Effect of Caffeine on the Bioavailability and Pharmacokinetics of an Acetylsalicylic Acid-Paracetamol Combination: Results of a Phase I Study.

ABSTRACT:

Introduction

Caffeine is used as an adjuvant in analgesic combinations to enhance their efficacy. The present study aimed to determine the effect of caffeine on the pharmacokinetics of acetylsalicylic acid (ASA) and paracetamol when used as a fixed-dose ASA/paracetamol/caffeine combination.

Methods

In this single-centre, two-way, cross-over phase I study, volunteers fasted overnight (??12 h) and randomly received single oral doses of 250 mg ASA/200 mg paracetamol (reference) or 250 mg ASA/200 mg paracetamol/50 mg caffeine (test). Blood samples were collected before and up to 24 h after dosing. The primary end points were the area under the concentration-time curve from zero to infinity (AUC_0-?) and maximum plasma concentration (C_max) for ASA, salicylic acid (SA) and paracetamol from the two combinations. The main secondary end points were AUC_0-? and C_max of caffeine and time to reach C_max (t_max) of all drugs.

Results

Eighteen healthy male volunteers (32.5?±?10.5 years) participated in the study. The geometric means of C_max for ASA, SA and paracetamol were similar in the test (3.71, 15.8 and 2.42 µg/ml, respectively) and reference groups (3.89, 15.8, 2.42 µg/ml, respectively). The geometric mean of AUC_0-? for ASA, SA and paracetamol from the test combination was 2.86, 60.5 and 7.68 µg h/ml, respectively, and that for the reference was 2.96, 59.1 and 7.77 µg h/ml, respectively. The medians of t_max for ASA, SA and paracetamol were similar between the two groups. The point estimates for the ratios of AUC_0-? and C_max for test versus reference regarding ASA, SA and paracetamol were within the predefined equivalence limits. The two treatments were well tolerated.

Conclusion

Caffeine did not affect the pharmacokinetics of ASA and paracetamol when used as an adjuvant in ASA/paracetamol fixed-dose combination under fasting conditions, suggesting that caffeine enhances the analgesic efficacy of these drugs by pharmacodynamic rather than pharmacokinetic interactions.

Funding

Sanofi-Aventis Deutschland GmbH.

SUBMITTER: Weiser T

PROVIDER: S-EPMC6824350 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Effect of Caffeine on the Bioavailability and Pharmacokinetics of an Acetylsalicylic Acid-Paracetamol Combination: Results of a Phase I Study.

Weiser Thomas T Weigmann Harald H

Advances in therapy 20190213 3

<h4>Introduction</h4>Caffeine is used as an adjuvant in analgesic combinations to enhance their efficacy. The present study aimed to determine the effect of caffeine on the pharmacokinetics of acetylsalicylic acid (ASA) and paracetamol when used as a fixed-dose ASA/paracetamol/caffeine combination.<h4>Methods</h4>In this single-centre, two-way, cross-over phase I study, volunteers fasted overnight (≥ 12 h) and randomly received single oral doses of 250 mg ASA/200 mg paracetamol (reference) or 25 ...[more]

PMID: 30758744

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Project description:The present paper continues a more complex research related to the increased synergism in terms of both anti-inflammatory and analgesic effect obtained by the addition of chlorpheniramine (CLF) to the common acetylsalicylic acid (ASA), acetaminophen (PAR), and caffeine (CAF) combination. This synergistic effect was previously highlighted both in vitro in rat models and in vivo in the treatment of migraine. The aim of the research was to further evaluate the analgesic effect of a synergistic low-dose ASA-PAR-CAF-CLF combination in the treatment of low back pain, in a parallel, multiple-dose, double-blind, active controlled clinical trial. A number of 89 patients with low back pain of at least moderate intensity were randomly assigned to receive Algopirin® (ALG), a combinational product containing 125 mg ASA, 75 mg PAR, 15 mg CAF, and 2 mg CLF, or PAR 500 mg, a drug recognized by American Pain Society as "safe and effective" in the treatment of low back pain. One tablet of the assigned product was administered three times a day for seven consecutive days. The patients evaluated their pain level using a Visual Analog Scale prior to administration, and at 1, 2, 4, and 6 h after the morning dose. Time course of effect was similar in structure and size for both treatments. Pain relief appeared rapidly and steadily increased over 4 h after drug administration. Differential pain curves of ALG and PAR were very similar and comparable with the previously determined ALG analgesia pattern in migraine. Differences between the daily mean pain scores were not statistically significant for the two treatments. Similar results were obtained for the Sum of Pain Intensity Differences (SPID) for 0-4 h and 0-6 h intervals as well as for the time course of the proportion of patients with at least 30% and at least 50% pain relief. In conclusion, in spite of very small doses of active components, ALG proved equally effective to the standard low back pain treatment and therefore a viable therapeutic alternative, mainly for patients with gastrointestinal and hepatic sensitivity. Trial Registration: www.ClinicalTrials.gov, identifier EudraCT No.: 2015-002314-74.

Dataset Information

Effect of Caffeine on the Bioavailability and Pharmacokinetics of an Acetylsalicylic Acid-Paracetamol Combination: Results of a Phase I Study.

Introduction

Methods

Results

Conclusion

Funding

Publications

Effect of Caffeine on the Bioavailability and Pharmacokinetics of an Acetylsalicylic Acid-Paracetamol Combination: Results of a Phase I Study.

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