CC BY-NC-ND 4.0 · Planta Med 2023; 89(02): 140-147
DOI: 10.1055/a-1821-8690
Biological and Pharmacological Activity
Original Papers

Food Interactions Observed in a Pharmacokinetic Investigation Comparing Two Marketed Cold Preparations (BNO1016 and ELOM-080) after Administration to Beagle Dogs – A Pilot Study

Jan Seibel
1   Bionorica SE, Dept. Clinical & Scientific Affairs R&D, Neumarkt i. d. O.Pf., Germany
Astrid Neumann
2   Bionorica Research GmbH, Dept. Bioanalytics, Innsbruck, Austria
Anne Müller
2   Bionorica Research GmbH, Dept. Bioanalytics, Innsbruck, Austria
1   Bionorica SE, Dept. Clinical & Scientific Affairs R&D, Neumarkt i. d. O.Pf., Germany
› Author Affiliations


Sinupret extract (BNO 1016) and Gelomyrtol forte (ELOM-080) represent the two top-selling cold remedies in Germany nowadays. Whereas BNO 1016 is a typical immediate release coated tablet, ELOM-080 is an enteric-coated soft gelatin capsule. The latter formulation, however, is at risk of pharmacokinetic interactions affecting absorption, especially in cases of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 were administered under fasting and fed conditions. Blood was sampled up to 30 h post-administration and plasma concentrations of the characteristic ingredients of BNO 1016 as well as ELOM-080 analytes were determined. Pharmacokinetic parameters focusing on the rate and extent of absorption were derived. BNO 1016 analytes demonstrated a similar course in both the fasted and fed states. ELOM-080 analytes also showed a similar picture in the fasted state. However, lag times (time from administration to first quantifiable time point in plasma) of up to 2 h post-administration with corresponding time to reach maximum concentration (obtained directly from the measured concentration) values of 3 to 4 h were observed, reflecting a longer gastric residence time. In the fed state, ELOM-080 showed significant pharmacokinetic characteristics, suggesting a clear food effect. A major observation was a double peak phenomenon that could be observed in two of three dogs. Furthermore, lag times of some analytes, up to 3 – 4 h, and corresponding time to reach maximum concentration values, up to 6 – 8 h, occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may also be a significant risk for food effects with ELOM-080 in humans.

Publication History

Received: 03 December 2021

Accepted after revision: 14 March 2022

Article published online:
06 May 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Mäder K. Innovative Arzneiformen: Ein Lehrbuch für Studium und Praxis [Innovative Dosage Forms: A Textbook for Study and Practice]. 1st edition. Stuttgart: Wissenschaftliche Verlagsgesellschaft Stuttgart; 2009
  • 2 Uhl P. Schnell oder langsam, wie sich die Freisetzung von Arzneimitteln modifizieren lässt [Fast or slow, how to modify the release of drugs]. DAZ 2019; 28: 44
  • 3 Bayrischer Apothekerverband. Marktdaten Selbstmedikation: Gesamtjahr 2020 [Self-medication Market Data: Full Year 2020]. OTC Manager 2021; 3: 8-33
  • 4 G. Pohl-Boskamp GmbH & Co. KG. Summary of product characteristics: Gelomyrtol forte. Approval No.: 6096046.00.00, Feb 2018. Accessed February 17, 2022 at:
  • 5 Han D, Wang N, Zhang L. The effect of myrtol standardized on human nasal ciliary beat frequency and mucociliary transport time. Am J Rhinol Allergy 2009; 23: 610-614
  • 6 Dorow P, Weiss T, Felix R, Schmutzler H. Effect of a secretolytic and a combination of pinene, limonene and cineole on mucociliary clearance in patients with chronic obstructive pulmonary disease. Arzneimittelforsch 1987; 37: 1378-1381
  • 7 Behrbohm H, Kaschke O, Sydow K. Effect of the phytogenic secretolytic drug Gelomyrtol forte on mucociliary clearance of the maxillary sinus. Laryngorhinootologie 1995; 74: 733-737
  • 8 Zhang S, Skinner D, Hicks SB, Bevensee MO, Sorscher EJ, Lazrak A, Matalon S, McNicholas CM, Woodworth BA. Sinupret activates CFTR and TMEM16A-dependent transepithelial chloride transport and improves indicators of mucociliary clearance. PLoS One 2014; 9: e104090
  • 9 Kreindler JL, Chen B, Kreitman Y, Kofonow J, Adams KM, Cohen NA. The novel dry extract BNO 1011 stimulates chloride transport and ciliary beat frequency in human respiratory epithelial cultures. Am J Rhinol Allergy 2012; 26: 439-443
  • 10 Virgin F, Zhang S, Schuster D, Azbell C, Fortenberry J, Sorscher EJ, Woodworth BA. The bioflavonoid compound, Sinupret, stimulates transepithelial chloride transport in vitro and in vivo . Laryngoscope 2010; 120: 1051-1056
  • 11 Bionorica SE. Summary of product characteristics: Sinupret extract. Approval No.: 84060.00.00, Jan 2018. Accessed February 17, 2022 at:
  • 12 Rossi A, Dehm F, Kiesselbach C, Haunschild J, Sautebin L, Werz O. The novel Sinupret dry extract exhibits anti-inflammatory effectiveness in vivo . Fitoterapia 2012; 83: 715-720
  • 13 Karim A, Burns T, Wearly L, Streicher J, Palmer M. Food-induced changes in theophylline absorption. from controlled-release formulations. Part I. Substantial increased and decreased absorption with Uniphyl tablets and Theo-Dur Sprinkle. Clin Pharmacol Ther 1985; 38: 77-83
  • 14 Karim A, Burns T, Janky D, Hurwitz A. Food-induced changes in theophylline absorption from controlled-release formulations. Part II. Importance of meal composition and dosing time relative to meal intake in assessing changes in absorption. Clin Pharmacol Ther 1985; 38: 642-647
  • 15 Waldman SA, Morganroth J. Effect of food on the bioequivalence of different verapamil sustained-release formulations. J Clin Pharmacol 1995; 35: 163-169
  • 16 Blume HH, Schug BS, Potthast H. Influence of food on the bioavailability of controlled/modified release products. In: Kuhlmann J, Weihrauch TR. eds. Clinical pharmacology 12, food–drug interactions. München, Bern, Wien, New York: Zuckschwerdt; 1996: 25-32
  • 17 Szurszewski JH. A migrating electric complex of the canine small intestine. Am J Physiol 1969; 217: 1757-1763
  • 18 Sjögren E, Abrahamsson B, Augustijns P, Becker D, Bolger MB, Brewster M, Brouwers J, Flanagan T, Harwood M, Heinen C, Holm R, Juretschke HP, Kubbinga M, Lindahl A, Lukacova V, Münster U, Neuhoff S, Nguyen MA, Peer Av. Reppas C, Hodjegan AR, Tannergren C, Weitschies W, Wilson C, Zane P, Lennernäs H, Langguth P. In vivo methods for drug absorption – comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects. Eur J Pharm Sci 2014; 57: 99-151
  • 19 Lentz KA. Current methods for predicting human food effect. AAPS J 2008; 10: 282-288
  • 20 Ewe K, Press AG, Bollen S, Schuhn I. Gastric emptying of indigestible tablets in relation to composition and time of ingestion of meals studied by metal detector. Digest Dis Sci 1991; 36: 146-152
  • 21 Davis SS, Hardy JG, Fara JW. The transit of pharmaceutical dosage forms through the small intestine. Gut 1986; 27: 886-892
  • 22 Hendeles L, Weinberger M, Milavetz G, Hill 3rd M, Vaughan L. Food-induced “dose-dumping” from a once-a-day theophylline product as a cause of theophylline toxicity. Chest 1985; 87: 758-765
  • 23 European Medicines Agency (EMA):. EMEA/CHMP/EWP/280/96 Rev1. Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms. November 2014. Accessed February 17, 2022 at:
  • 24 Schug BS, Brendel E, Chantraine E, Wolf D, Martin W, Schall R, Blume HH. The effect of food on the pharmacokinetics of nifedipine in two slow release formulations: pronounced lag-time after a high fat breakfast. J Clin Pharmacol 2002; 53: 582-588
  • 25 Aoyagi N, Ogata H, Kaniwa N, Uchiyama M, Yasuda Y, Tanioka Y. Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits. J Pharm Sci 1992; 81: 1170-1174
  • 26 Ramkumar D, Schulze KS. The pylorus. Neurogastroenterol Motil 2005; 17: 22-30
  • 27 European Medicines Agency (EMA):. EMEA/CHMP/EWP/192217/2009. Guideline on bioanalytical method validation. February 2012. Accessed February 17, 2022 at: