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dc.contributor.authorGerber, Werner
dc.contributor.authorHamman, Josias H.
dc.contributor.authorSteyn, Johan D.
dc.date.accessioned2018-03-14T12:17:34Z
dc.date.available2018-03-14T12:17:34Z
dc.date.issued2018
dc.identifier.citationGerber, W. et al. 2018. Excipient-drug pharmacokinetic interactions: effect of disintegrants on efflux across excised pig intestinal tissues. Journal of food and drug analysis, 26(2)(Suppl): S115-S124. [https://doi.org/10.1016/j.jfda.2018.01.007]en_US
dc.identifier.issn1021-9498
dc.identifier.urihttp://hdl.handle.net/10394/26589
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S1021949818300358
dc.identifier.urihttps://doi.org/10.1016/j.jfda.2018.01.007
dc.description.abstractPharmaceutical excipients were designed originally to be pharmacologically inert. However, certain excipients were found to have altering effects on drug pharmacodynamics and/or pharmacokinetics. Pharmacokinetic interactions may be caused by modulation of efflux transporter proteins, intercellular tight junctions and/or metabolic enzyme amongst others. In this study, five disintegrants from different chemical classes were evaluated for P-glycoprotein (P-gp) related inhibition and tight junction modulation effects. Bi-directional transport studies of the model compound, Rhodamine 123 (R123) were conducted in the absence (control group) and presence (experimental groups) of four concentrations of each selected disintegrant across excised pig jejunum tissue. The results showed that some of the selected disintegrants (e.g. Ac-di-sol® and Kollidon® CL-M) increased R123 absorptive transport due to inhibition of P-gp related efflux, while another disintegrant (e.g. sodium alginate) changed R123 transport due to inhibition of P-gp in conjunction with a transient opening of the tight junctions in a concentration dependent way. It may be concluded that the co-application of some disintegrants to the intestinal epithelium may lead to pharmacokinetic interactions with drugs that are susceptible to P-gp related efflux. However, the clinical significance of these in vitro permeation findings should be confirmed by means of in vivo studiesen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectDisintegrantsen_US
dc.subjectExcipienten_US
dc.subjectEx vivoen_US
dc.subjectP-glycoproteinen_US
dc.subjectPharmacokinetic interactionsen_US
dc.subjectRhodamine 123en_US
dc.titleExcipient-drug pharmacokinetic interactions: effect of disintegrants on efflux across excised pig intestinal tissuesen_US
dc.typeArticleen_US
dc.contributor.researchID10081097 - Hamman, Josias Hendrik
dc.contributor.researchID12297305 - Steyn, Johan Dewald
dc.contributor.researchID22117040 - Gerber, Werner


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