Skip to main content

13.02.2019 | Original Research | Ausgabe 3/2019 Open Access

Advances in Therapy 3/2019

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

Advances in Therapy > Ausgabe 3/2019
Thomas Weiser, Harald Weigmann
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s12325-019-0891-5) contains supplementary material, which is available to authorized users.

Enhanced Digital Features

To view enhanced digital features for this article go to https://​doi.​org/​10.​6084/​m9.​figshare.​7558871.



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.


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 (AUC0–∞) and maximum plasma concentration (Cmax) for ASA, salicylic acid (SA) and paracetamol from the two combinations. The main secondary end points were AUC0–∞ and Cmax of caffeine and time to reach Cmax (tmax) of all drugs.


Eighteen healthy male volunteers (32.5 ± 10.5 years) participated in the study. The geometric means of Cmax 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 AUC0–∞ 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 tmax for ASA, SA and paracetamol were similar between the two groups. The point estimates for the ratios of AUC0–∞ and Cmax for test versus reference regarding ASA, SA and paracetamol were within the predefined equivalence limits. The two treatments were well tolerated.


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.


Sanofi-Aventis Deutschland GmbH.

Unsere Produktempfehlungen

e.Med Interdisziplinär


Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag als Mediziner

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf

Jetzt e.Med zum Sonderpreis bestellen!

e.Med Innere Medizin


Mit e.Med Innere Medizin erhalten Sie Zugang zu CME-Fortbildungen des Fachgebietes Innere Medizin, den Premium-Inhalten der internistischen Fachzeitschriften, inklusive einer gedruckten internistischen Zeitschrift Ihrer Wahl.

Jetzt e.Med zum Sonderpreis bestellen!

e.Med Allgemeinmedizin


Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.

Jetzt e.Med zum Sonderpreis bestellen!

Über diesen Artikel

Weitere Artikel der Ausgabe 3/2019

Advances in Therapy 3/2019 Zur Ausgabe

Neu im Fachgebiet Innere Medizin

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Innere Medizin und bleiben Sie gut informiert – ganz bequem per eMail.

© Springer Medizin