INFLUENCE OF POMEGRANATE JUICE ON THE CYP3A4-MEDIATED METABOLISM AND P-GLYCOPROTEIN MEDIATED TRANSPORT OF SAQUINAVIR IN VIVO AND EX VIVO MODELS
Abstract: 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<0.001) may be
due to inhibition of CYP3A4 and P-gp. But interestingly, the Cmax and AUC0-24
of saquinavir was decreased significantly with PGJ in MDS. This is may be due
to induction of CYP3A4. The transport of saquinavir was increased in presence
of PGJ and known P-gp inhibitors (Verapamil, Ketoconazole and Quinindine)
across the rat everted gut sacs ex vivo. The present study results suggested
that PGJ has both effects (inhibition, in SDS and induction, in MDS) on
CYP3A4-mediated saquinavir metabolism in vivo and inhibitory effect on the P-gp
mediated intestinal transport of saquinavir ex vivo. Further studies are needed
to confirm this interaction at cellular level using cell lines and in humans.
Author: Sridhar Vemulapalli
Journal Code: jpfarmasigg160037

Artikel Terkait :
Jp Farmasi gg 2016
- NATIONAL HEALTH COVERAGE SYSTEM : PHARMACISTS AND JKN PARTICIPANT SATISFACTION IN PRIMARY HEALTH FACILITIES
- Validation and Quantification of Theophylline and Salbutamol using Ion Pair Liquid Chromatography
- SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-[(SUBSTITUEDPHENYL)-5-(1-PHENYL-3-(PIPERAZINYL)PYRIDO[3,2-f]QUINAZOLIN-4(1H)-YL]-1,3,4-THIADIAZOLES
- EVALUATION OF THE EFFECTIVENESS OF FREE NICOTINE PATCH THERAPY IN A CHARITY CLINIC FOR SMOKING CESSATION
- Ameliorative effects of vitamins C and E on tenofovir/nevirapine-induced hepatorenal oxidative stress in albino rats
- FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES OF ATENOLOL
- Modulatory effect of Drosera peltata J.E.Sm on development of metabolic syndrome in tumor bearing mice
- COMPARATIVE STANDARDIZATION OF MARKETED FORMULATIONS OF FERMENTED BIOMEDICINE – ARJUNARISTHA
- ANTIOXIDANT ACTIVITY OF DRIED STRAWBERRY JUICES (Fragaria vesca L.) EMULGEL PREPARATION USING CANDLENUT OIL AND IT’S DIFFUSION
- ANTIDIABETIC ACTIVITY OF ETHANOLIC EXTRACT OF KALANCHOE PINNATA LEAVES IN ALLOXAN INDUCED HYPERGLYCAEMIC RATS
- MONOSODIUM GLUTAMATE EXPOSURE AT EARLY DEVELOPMENTAL STAGE INCREASES APOPTOSIS AND STEREOTYPIC BEHAVIOR RISKS ON ZEBRAFISH (DANIO RERIO) LARVAE
- THE EFFICACY OF DIFFERENT ORAL MAGNESIUM SUPPLEMENTS FOR MIGRAINE PREVENTION: A LITERATURE REVIEW
- OPTIMIZING STRUCTURE-BASED VIRTUAL SCREENING PROTOCOL TO IDENTIFY PHYTOCHEMICALS AS CYCLOOXYGENASE-2 INHIBITORS
- FORMULATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM OF BOVINE SERUM ALBUMIN USING HLB (HYDROPHILIC-LYPOPHILIC BALANCE) APPROACH
- CYTOTOXIC AND ANTI-VIRAL ACTIVITY OF Acacia catechu ON HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS
- SYNTHESIS AND ANALGETIC ACTIVITY EVALUATION OF 4-[N-(4-HYDROXYPHENYL)CARBOXYMIDOYL]-2-METHOXYPHENOL
- SYNTHESIS AND SCREENING OF SOME AZOMETHINES BEARING METHYL SALICYLATE MOIETY FOR ANTIBACTERIAL ACTIVITIES
- AN LC- MS/MS METHOD FOR THE DETERMINATION OF OMEPRAZOLE ON PROTON PUMP INHIBITOR IN HUMAN PLASMA
- ANTI-OXIDANT AND ANTI-DIABETIC ACTIVITIES OF ETHANOLIC EXTRACT OF Primula denticulata FLOWERS
- ANTIUROLITHIATIC ACTIVITY OF ETHANOLIC EXTRACT OF TAXILLUS TOMENTOSUS PLANT ON ETHYLENE GLYCOL AND AMMONIUM CHLORIDE INDUCED UROLITHIASIS IN WISTAR RATS
- PHYTOCHEMICAL CONSTITUENTS AND HYPOGLYCEMIC EFFECT OF GYMNEMIC ACID EXTRACTS FROM BIG AND SMALL LEAF VARIETIES OF Gymnema Sylvestre R.Br
- FORMULATION DEVELOPMENT AND CHARACTERIZATION OF TEA TREE OIL LOADED ETHOSOMES
- DETERMINATION OF SIBUTRAMINE ADULTERATED IN HERBAL SLIMMING PRODUCTS USING TLC DENSITOMETRIC METHOD
- PHYSICAL CHARACTERIZATION OF IBUPROFEN-STEARIC ACID BINARY MIXTURE DUE TO COMPRESSION FORCE