Combined effect of rifampicin-induced P-glycoprotein expression and lipopolysaccharide-induced intestinal sepsis on the effective permeability and pharmacokinetics of an anti-malarial candidate CDRI 97/78 in rats
| العنوان: | Combined effect of rifampicin-induced P-glycoprotein expression and lipopolysaccharide-induced intestinal sepsis on the effective permeability and pharmacokinetics of an anti-malarial candidate CDRI 97/78 in rats |
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| المؤلفون: | Shio Kumar Singh, Jampala Krishna, Yeshwant Singh, Mahendra Kumar Hidau |
| المصدر: | Xenobiotica. 45:731-740 |
| بيانات النشر: | Informa UK Limited, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Lipopolysaccharides, Male, Drug, ATP Binding Cassette Transporter, Subfamily B, Lipopolysaccharide, Health, Toxicology and Mutagenesis, media_common.quotation_subject, Biological Availability, Pharmacology, Toxicology, Biochemistry, Permeability, Intestinal absorption, Rats, Sprague-Dawley, Sepsis, Antimalarials, chemistry.chemical_compound, Pharmacokinetics, medicine, Animals, Intestinal Mucosa, P-glycoprotein, media_common, biology, General Medicine, Bridged Bicyclo Compounds, Heterocyclic, medicine.disease, Rats, Bioavailability, Intestinal Absorption, chemistry, biology.protein, Rifampin, Rifampicin, medicine.drug |
| الوصف: | 1. The study aimed to investigate the influences on the pharmacokinetics (PK) of an anti-malarial drug 97/78 in rats pretreated with orally administered rifampicin and bacterial endotoxin lipopolysaccharide (LPS). 2. In-situ intestinal absorption studies were conducted on rats pretreated with rifampicin and LPS or both to estimate effective permeability (Peff) of 97/78. In-vivo studies were then conducted to explore 97/78 PK profile under these conditions. In-situ studies revealed that Peff value decreased to 64% (2.7 ± 0.6) × 10(-4 )cm/s in rats pretreated with rifampicin. This decrease was further enhanced very significantly to 4.5% (0.19 ± 0.03) × 10(-4 )cm/s in rats pretreated both with rifampicin and LPS (p0.05). For PK studies, it was found that relative bioavailability (RB) was decreased to 22.56% in rifampicin-pretreated rats and to 8.02% in rats pretreated both with rifampicin and LPS. About five-fold decrease was observed in systemic exposure (AUC) of 97/78 in rifampicin-pretreated rats. This decrease was further augmented to 12-fold upon rifampicin and LPS pretreatment. 3. Orally administered rifampicin decreased the concentration of 97/78 in circulation. This decrease was further enhanced significantly to a very low level by LPS-induced intestinal sepsis. |
| تدمد: | 1366-5928 0049-8254 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd07e125782e0bdbd7679d6969e20f3a https://doi.org/10.3109/00498254.2015.1017548 |
| رقم الأكسشن: | edsair.doi.dedup.....fd07e125782e0bdbd7679d6969e20f3a |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 13665928 00498254 |
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