Food interactions observed in a pharmacokinetic investigation comparing two marketed cold preparations (BNO1016 and ELOM-080) after administration to male beagle dogs

The cold remedies 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 the case of concomitant food intake. In the present pilot study, we investigated the risk of a possible food effect on BNO 1016 in comparison to ELOM-080 in three male beagle dogs. Single doses of BNO 1016 and ELOM-80 at 80 mg/kg and 160 mg/kg, respectively, were administered under fasting and fed conditions according to a 4-period, 4-treatment within-design. Blood sampling took place until up to 30 h p.a. and plasma concentrations of gentiopicroside, verbenalin and from a further marker analyte (BNO 1016 analytes) as well as 1,8-cineole, limonene and perillic acid (ELOM-080 analytes) were determined. Pharmacokinetic parameters focusing on rate and extent of absorption were derived. BNO 1016 analytes demonstrated a homogenous course in all animals in both, the fasted and fed state. Pharmacokinetic characteristics of a typical immediate release drug formulation were observed for all analytes and a food effect could be ruled out. ELOM-080 analytes also showed a homogeneous picture in the fasted state. However, lag-times (tlag) of up to 2 h p.a. with corresponding tmax values of 3 to 4 h were observed, reflecting a longer gastric residence time of the formulation. 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 out of three dogs. Furthermore, lag-times of some analytes up to 3-4 h and corresponding tmax values of up to 6-8 h occurred. In contrast to BNO 1016, these findings suggest that, as with other enteric-coated formulations, there may be a significant risk for food effects with ELOM-080 also in humans. ### Competing Interest Statement Jan Seibel and Meinolf Wonnemann are employees of Bionorica SE, Germany. Astrid Neumann and Anne Mueller are employees of Bionorica research GmbH, Austria * API : active pharmaceutical ingredient AUC(0-tlast) : area under the plasma concentration vs . time curve from dosing time to the last measurement time point with a concentration value above the lower limit of quantitation, calculated by means of the linear/log trapezoidal method which uses the linear trapezoidal rule up to Cmax and afterwards the log(interpolation) trapezoidal rule for the subsequent part of the curve Cmax : maximum concentration in plasma, directly taken from measured concentration values EMA : European Medicines Agency GC-MS : gas chromatography coupled to mass spectrometry LC-MS/MS : liquid chromatography coupled to mass spectrometry LLOQ : lower limit of quantification MMC : migrating motor complex p.a. : post administration SmPC : Summary of product characteristics tlag : time from administration to first quantifiable time point in plasma tmax : time to reach maximum concentration, obtained directly from measured values t1/2 : apparent terminal elimination half-life