INFLUENCE OF POMEGRANATE JUICE ON THE CYP3A4-MEDIATED METABOLISM AND P-GLYCOPROTEIN MEDIATED TRANSPORT OF SAQUINAVIR IN VIVO AND EX VIVO MODELS
| Autor: | Sridhar Vemulapalli, Surya Sandeep Mullapudi, Ravindrababu Pingili, Ramya Kothapalli, Sivaramakrishna Kondru, Naveenbabu Kilaru |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Indonesian Journal of Pharmacy, Vol 27, Iss 3, Pp 152-162 (2016) |
| Druh dokumentu: | article |
| ISSN: | 2338-9427 2338-9486 |
| DOI: | 10.14499/indonesianjpharm27iss3pp152 |
| Popis: | Cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) play an important role in the first pass metabolism thereby limits the oral bioavailability of many clinically important and frequently prescribed drugs. The absolute oral bioavailability of saquinavir is very low (i. e. 4%) due to its extensive first pass metabolism by the major metabolizing isozyme CYP3A4 and it is also a substrate of P-gp. Pomegranate juice (PGJ) was known to be a modulator of CYP3A4 and P-gp. Therefore, the aim of this study was to evaluate the influence of PGJ on the pharmacokinetics (PK) of saquinavir in wistar rats and on the P-gp mediated intestinal transport of saquinavir in everted gut sacs ex vivo. Rats were treated orally with saquinavir (100 mg/kg) alone and in combination with PGJ (0.5, 1.0 and 2.0 mL/200g, body weight) for 15 consecutive days. Blood samples were collected on 1st day in single dose pharmacokinetic study (SDS) and on 15th day in multiple dose pharmacokinetic study (MDS). The peak plasma concentration (Cmax)and area under the plasma concentration-time curve (AUC0-24) of saquinavir was increased with PGJ in SDS (p |
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