Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Martin Lau Christiansen; Rene Holm; Bertil Abrahamsson; Jette Jacobsen; Jakob Kristensen; Jens Rikardt Andersen; Anette Müllertz

doi:10.1016/j.ejps.2016.01.011

Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Martin Lau Christiansen, Rene Holm, Bertil Abrahamsson, Jette Jacobsen, Jakob Kristensen, Jens Rikardt Andersen, Anette Müllertz

Nutrition and Health

20 Citations (Scopus)

Abstract

Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.

Original language	English
Journal	European Journal of Pharmaceutical Sciences
Volume	84
Pages (from-to)	77-82
Number of pages	6
ISSN	0928-0987
DOIs	https://doi.org/10.1016/j.ejps.2016.01.011
Publication status	Published - 10 Mar 2016

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Christiansen, M. L., Holm, R., Abrahamsson, B., Jacobsen, J., Kristensen, J., Andersen, J. R., & Müllertz, A. (2016). Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers. European Journal of Pharmaceutical Sciences, 84, 77-82. https://doi.org/10.1016/j.ejps.2016.01.011

Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers. / Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil et al.

In: European Journal of Pharmaceutical Sciences, Vol. 84, 10.03.2016, p. 77-82.

Research output: Contribution to journal › Journal article › Research › peer-review

Christiansen, ML, Holm, R, Abrahamsson, B, Jacobsen, J, Kristensen, J, Andersen, JR & Müllertz, A 2016, 'Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers', European Journal of Pharmaceutical Sciences, vol. 84, pp. 77-82. https://doi.org/10.1016/j.ejps.2016.01.011

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abstract = "Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy{\textregistered}, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy{\textregistered}) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.",

author = "Christiansen, {Martin Lau} and Rene Holm and Bertil Abrahamsson and Jette Jacobsen and Jakob Kristensen and Andersen, {Jens Rikardt} and Anette M{\"u}llertz",

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AU - Christiansen, Martin Lau

AU - Holm, Rene

AU - Abrahamsson, Bertil

AU - Jacobsen, Jette

AU - Kristensen, Jakob

AU - Andersen, Jens Rikardt

AU - Müllertz, Anette

N1 - CURIS 2016 NEXS 045

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N2 - Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.

AB - Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol.

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DO - 10.1016/j.ejps.2016.01.011

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SN - 0928-0987

VL - 84

SP - 77

EP - 82

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

ER -

Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

Abstract

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