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Evidence for time-dependent interactions between Ritonavir and Lopinavir/Ritonavir plasma levels following P-Glycoprotein inhibition in Sprague-Dawley rats

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dc.contributor.author Rheeders, Malie
dc.contributor.author Viljoen, Michelle
dc.contributor.author Du Plooy, Michael
dc.date.accessioned 2012-09-10T16:29:39Z
dc.date.available 2012-09-10T16:29:39Z
dc.date.issued 2011
dc.identifier.citation Du Plooy, M. et al. 2011. Evidence for time-dependent interactions between Ritonavir and Lopinavir/Ritonavir plasma levels following P-Glycoprotein inhibition in Sprague-Dawley rats. Biological & pharmaceutical bulletin, 34(1):66-70. [https://www.jstage.jst.go.jp/browse/bpb] en_US
dc.identifier.issn 0918-6158
dc.identifier.issn 1347-5215 (Online)
dc.identifier.uri http://hdl.handle.net/10394/7378
dc.description.abstract The interaction between verapamil, a P-glycoprotein (P-gp) inhibitor, with ritonavir and lopinavir/ritonavir (LPV/r) after acute and chronic treatment was investigated in rats. Rats were divided into 4 groups, viz. Group 1: ritonavir, 20 mg/kg/d (n_18), group 2: ritonavir, 20 mg/kg/d plus verapamil 5 mg/kg/d (n_18), group 3: LPV/r, 80 and 20 mg/kg/d (n_17) and group 4: LPV/r, 80 and 20 mg/kg/d plus verapamil 5 mg/kg/d (n_18). Blood samples were collected after decapitation on days 1, 7 and 21. Lopinavir and ritonavir plasma levels were simultaneous determined by a validated LC/MS/MS method. The lower limit of quantification for both ritonavir and lopinavir was 0.078m g/ml.Verapamil significantly increased ritonavir plasma levels, administered as monotherapy, following acute (p_0.005) and chronic treatment (day 21) (p_0.005). During acute (but not chronic) LPV/r treatment, verapamil also increased the lopinavir levels (p_0.05). A time or exposure dependent pharmacokinetic interaction was thus observed between verapamil and ritonavir whether administered alone or after the lopinavir-ritonavir combination (LPV/r). This interaction occurred most prominently after acute treatment, and became less pronounced over time. This study indicates the importance of a longer time frame to investigate enzyme based drug interactions in rat models. en_US
dc.language.iso en en_US
dc.publisher Pharmaceutical Society of Japan en_US
dc.subject Animal model en_US
dc.subject P-glycoprotein inhibition en_US
dc.subject Lopinavir en_US
dc.subject Ritonavir en_US
dc.subject pharmacokinetic interaction complex III deficiency en_US
dc.title Evidence for time-dependent interactions between Ritonavir and Lopinavir/Ritonavir plasma levels following P-Glycoprotein inhibition in Sprague-Dawley rats en_US
dc.type Article en_US


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