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Sex differences in excipient effects: Enhancement in ranitidine bioavailability in the presence of polyethylene glycol in male, but not female, rats

Afonso-Pereira, F; Murdan, S; Sousa, J; Veiga, F; Basit, AW; (2016) Sex differences in excipient effects: Enhancement in ranitidine bioavailability in the presence of polyethylene glycol in male, but not female, rats. International Journal of Pharmaceutics , 506 (1-2) pp. 237-241. 10.1016/j.ijpharm.2016.04.022. Green open access

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Abstract

Males and females respond differently to drugs: indeed, sex plays a crucial role in determining drug pharmacokinetics and pharmacodynamics. Excipients have also been shown to enhance the biovailability of drugs differently in men and women. The aim of this work was to investigate whether rodents are a good model in which to study sex-specific effects of polyethylene glycol 400 (PEG 400) on the bioavailability of ranitidine. Ranitidine (50mg/Kg) was dissolved in water with different amounts of PEG 400 - 0 (control), 13, 26, 51, 77, 103, and 154mg/Kg; these solutions were dosed orally by gavage to male and female Wistar rats. Blood samples were withdrawn over 480minutes and assayed via HPLC-UV. Individual ranitidine plasma profiles were constructed for each rat, and standard pharmacokinetic parameters were determined. In the male rats, the change in the area under the plasma ranitidine curve (AUC0-480) compared to the control group, was +18%; +49% (p<0.05); +37% (p<0.05); +31% (p<0.05); +8% and -22% (p<0.05) for PEG 400 doses of 13; 26; 51; 77; 103; and 154mg/Kg respectively. On the other hand, females showed no statistically significant difference between the groups. In conclusion, low doses of PEG 400 enhanced the bioavailability of ranitidine in male, but not female, rats. These findings are in agreement with previously published human data, therefore confirming he validity of the rodent model, and highlight the unusual and clinically significant phenomenon that an excipient can influence drug bioavailability in one gender and not the other.

Type: Article
Title: Sex differences in excipient effects: Enhancement in ranitidine bioavailability in the presence of polyethylene glycol in male, but not female, rats
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ijpharm.2016.04.022
Publisher version: http://dx.doi.org/10.1016/j.ijpharm.2016.04.022
Language: English
Additional information: Copyright © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0.
Keywords: bioavailability, gender, p-glycoprotein, polyethylene glycol 400, polyoxyethylene polymers, ranitidine
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: http://discovery.ucl.ac.uk/id/eprint/1482617
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