G Bridger
Rega Institute for Medical Research
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Featured researches published by G Bridger.
International Journal of Pharmaceutics | 1999
J. Van Gelder; Myriam Witvrouw; Christophe Pannecouque; G Henson; G Bridger; Lieve Naesens; E. De Clercq; Pieter Annaert; M Shafiee; G. Van den Mooter; Renaat Kinget; Patrick Augustijns
9-(2-phosphonyomethoxypropyl)adenine (PMPA) and AMD3100 are highly potent and selective antiretroviral agents. Since PMPA is negatively charged and AMD3100 positively charged at physiological pH, their transepithelial transport and their potential for oral drug delivery is very low. In this study, ion pair formation was evaluated as a possible strategy to enhance transepithelial transport of PMPA and AMD3100. Positively charged counter ions such as t-hexyl-, t-heptyl-, t-octylammonium bromide and dodecyl-, tetradecyl-, hexadecyltrimethylammonium bromide were used to form ion pairs with PMPA, while sodium taurodeoxycholate (in vitro experiments) and sodium taurocholate (in vivo experiments) were used as counter ions for AMD3100. The effect of counter ions on transepithelial transport of PMPA (1 mM) and AMD3100 (1 mM) was investigated by measuring the flux across Caco-2 monolayers. An enhancement in drug transport could be observed at a concentration of 2 mM of hexadecyltrimethylammonium bromide (counter ion for PMPA) and 10 mM of sodium taurodeoxycholate (counter ion for AMD3100), but at the concentrations used, the absorption enhancing effect could be attributed to a reduction of the integrity of the monolayers. When AMD3100 transport was tested at a concentration of 200 microM, no flux was observed, even in the presence of relatively high concentrations of counter ion (20 times the concentration of AMD3100). Results obtained from partitioning studies of the drugs in the presence or absence of counter ion revealed that competition by other ions was responsible for the absence of an effect: when pure water was used as the aqueous phase, a reduction up to 24.4+/-1.4% and 17.0+/-1.3% of the initial aqueous concentration was observed for PMPA and AMD3100, respectively; however, as soon as other ions were present in the aqueous phase, the effect of the counter ion was diminished (25-50 mOsm) or completely abolished (270-305 mOsm). The absorption enhancing effect of counter ions was also studied in vivo: pharmacokinetic studies in rabbits showed that the oral bioavailability of AMD3100 in the presence of 4 equivalents of taurocholic acid remained very low and was only 3.2-fold better (i.e. 3.6%) in comparison to pure AMD3100. In view of the results obtained in the Caco-2 system, this absorption enhancement can be attributed to an effect on monolayer integrity rather than to the potential to form ion pairs. We can conclude that the formation of ion pairs may not be very efficient as a strategy to enhance transepithelial transport of charged hydrophilic compounds, as competition by other ions may abolish the beneficial effect of counter ions.
Molecular Pharmacology | 1999
José A. Esté; Cecilia Cabrera; Erik De Clercq; Sofie Struyf; Jo Van Damme; G Bridger; Renato T. Skerlj; Michael J. Abrams; Geoffrey Henson; Arantxa Gutierrez; Bonaventura Clotet; Dominique Schols
Abstract book | 2003
Dominique Schols; Sandra Claes; Sigrid Hatse; Katrien Princen; Kurt Vermeire; Erik De Clercq; Renato Skerlj; G Bridger; Gary Calandra
Abstract book | 2004
Dominique Schols; Kurt Vermeire; Sigrid Hatse; Katrien Princen; Erik De Clercq; Gary Calandra; Simon P. Fricker; Kim L. Nelson; Jean Labrecque; David Surrey Bogucki; Yuanxi Zhou; Renato Skerlj; G Bridger
Abstract book | 2005
Dominique Schols; Kurt Vermeire; S Fransen; W Huang; J Toma; J Whitcomb; C Petropoulos; Gary Calandra; G Bridger
Antiviral Research | 2004
Kurt Vermeire; Sigrid Hatse; Katrien Princen; Erik De Clercq; Gary Calandra; Renato Skerlj; G Bridger; Dominique Schols
Antiviral Research | 2004
Dominique Schols; Kurt Vermeire; Sigrid Hatse; Katrien Princen; Erik De Clercq; Gary Calandra; Simon P. Fricker; Kim L. Nelson; Jean Labrecque; David Surrey Bogucki; Yuanxi Zhou; Renato Skerlj; G Bridger
Antiviral Research | 1992
Erik De Clercq; N Yamamoto; Rudi Pauwels; Masanori Baba; Dominique Schols; Hiroshi Nakashima; Jan Balzarini; Zeger Debyser; Ba Murrer; D Schwartz; D Thornton; G Bridger; Simon P. Fricker; G Henson; M Abrams; D Picker
Abstract book | 2006
Kurt Vermeire; Thomas W. Bell; G Bridger; Dominique Schols
Journal of Biological Regulators and Homeostatic Agents | 2004
Katrien Princen; Sigrid Hatse; Kurt Vermeire; G Bridger; Erik De Clercq; Dominique Schols