P-glycoprotein limits the absorption of the anti-HIV drug zidovudine through rat intestinal segments

Quevedo, Mario Alfredo; Nieto, Leandro E.; Briñón, Margarita C.

doi:10.1016/j.ejps.2011.04.007

Cited by 28 publications

(24 citation statements)

References 41 publications

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“…The presence of VER did not affect the permeation of SD (p>0.05). VER is a known P-gp inhibitor that blocks the efflux pump and improves AZT permeation (Quevedo et al, 2011). These findings alerted us to the similarities between the P-pg blocking effects of VER and carrier polymers.…”

Section: Resultsmentioning

confidence: 89%

“…To evaluate the influence of P-gp on AZT permeability, the same assay described above was performed with the addition of 50 µg/mL of VER added to the medium (Quevedo et al, 2011). The tests were replicated six times.…”

Section: Intestinal Permeability and P-glycoprotein Influencementioning

confidence: 99%

“…The intestinal permeability of AZT was evaluated using the everted gut sac model described by Barthe et al (1998a) with modifications purposed by Quevedo et al (2011). The animals were handled in accordance with the guide for the care and use of experimental animals (CEUA/ UFSCAR Ethics in Research Committee, nº 003/2011).…”

Section: Intestinal Permeability and P-glycoprotein Influencementioning

confidence: 99%

See 2 more Smart Citations

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

Pedreiro

Cury

Chaud

et al. 2016

Braz. J. Pharm. Sci.

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Zidovudine (AZT) mucoadhesive solid dispersions (SD) were prepared using a sodium starch glycolate (SSG) and hypromellose phthalate (HPMCP) mixtures as carrier to enhance the intestinal permeability and bioavailability of zidovudine. SDs were prepared using the co-precipitation method followed by solvent evaporation and characterized according to their physicochemical properties such as particle size, crystallinity, thermal behavior, and liquid uptake ability. In vitro drug dissolution, mucoadhesiveness and AZT intestinal permeability were also determined. Thermal behavior and X-ray diffraction patterns demonstrated the amorphous state of AZT in SD systems. The HPMCP polymer restricted the liquid uptake ability in the acid medium; however, this property significantly increased with higher pH values. SDs allowed drug dissolution to occur in a controlled manner. HPMCP decreased the dissolution rates in the acid medium. The mucoadhesiveness of SDs was demonstrated and the permeability of AZT carried in solid dispersions was significantly improved. The effect of the SD carrier polymers on blocking efflux pump can be an important approach to improve the bioavailability of AZT.Uniterms: Zidovudine. Solid dispersion. Mucoadhesion. P-glycoprotein. Intestinal permeability.

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Section: Resultsmentioning

confidence: 89%

Section: Intestinal Permeability and P-glycoprotein Influencementioning

confidence: 99%

Section: Intestinal Permeability and P-glycoprotein Influencementioning

confidence: 99%

See 1 more Smart Citation

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

Pedreiro

Cury

Chaud

et al. 2016

Braz. J. Pharm. Sci.

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show abstract

“…58 The absolute oral bioavailability of AZT is reported to be approximately 75% in HIV-infected patients with mild hepatic disease. [59][60][61][62] Val ester of AZT (Val-AZT) was synthesized, and the higher membrane permeability, rapid conversion to AZT, and higher cellular uptake of Val-AZT were observed in CHO cells transfected with PEPT1 and Caco-2 cells transfected with PEPT1, indicating that the transport of Val-AZT is mediated predominantly by PEPT1 and Val-AZT is rapidly converted to the active parent drug, AZT, by the intracellular hydrolysis. 21,22 Cytarabine…”

Section: D-amphetaminementioning

confidence: 97%

A Minireview: Usefulness of Transporter-Targeted Prodrugs in Enhancing Membrane Permeability

Murakami

2016

Journal of Pharmaceutical Sciences

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Orally administered drugs are categorized into 4 classes depending on the solubility and permeability in a Biopharmaceutics Classification System. Prodrug derivatization is one of feasible approaches in modifying the physicochemical properties such as low solubility and low permeability without changing the in vivo pharmacological action of the parent drug. In this article, prodrug-targeted solute carrier (SLC) transporters were searched randomly by PubMed. Collected SLC transporters are amino acid transporter 1, bile acid transporter, carnitine transporter 2, glucose transporter 1, peptide transporter 1, vitamin C transporter 1, and multivitamin transporter. The usefulness of transporter-targeted prodrugs was evaluated in terms of membrane permeability, stability under acidic condition, and conversion to the parent drug. Among prodrugs collected, peptide transporter-targeted prodrugs exhibited the highest number, and some prodrugs such as valaciclovir and valganciclovir are clinically available. ATP-binding cassette efflux transporter, P-glycoprotein (P-gp), reduces the intestinal absorption of lipophilic P-gp substrate drugs, and SLC transporter-targeted prodrugs of P-gp substrate drugs circumvented the P-gp-mediated efflux transport. Thus, SLC transporter-targeted prodrug derivatization seems to be feasible approach to increase the oral bioavailability by overcoming various unwanted physicochemical properties of orally administered drugs, although the effect of food on prodrug absorption should be taken into consideration.

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“…Preparation of ATV NPs as per experimental design ATV-loaded Eudragit RL 100 NPs were prepared based on the method of nanoprecipitation as previously described, using Ultra Turrax IKA T25 digital high shear homogenizer (Quevedo et al, 2011;Singh & Pai, 2014a&b). In brief, 100 mg Eudragit RL 100 and weighed amount of ATV were dissolved in 30 ml acetone to form the organic phase.…”

Section: Hplc Methods Developmentmentioning

confidence: 99%

Atazanavir-loaded Eudragit RL 100 nanoparticles to improve oral bioavailability: optimization andin vitro/in vivoappraisal

Singh

Pai

2014

Drug Delivery

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Atazanavir (ATV) is a HIV protease inhibitor. Due to its intense lipophilicity, the oral delivery of ATV encounters several problems such as poor aqueous solubility, pH-dependent dissolution, rapid first-pass metabolism in liver by CYP3A5, which result in low bioavailability. To overcome afore mentioned limitations, ATV-loaded Eudragit RL100 nanoparticles (ATV NPs) were prepared to enhance oral bioavailability. ATV NPs were prepared by nanoprecipitation method. The ATV NPs were systematically optimized (OPT) using 3 2 central composite design (CCD) and the OPT formulation located using overlay plot. The pharmacokinetic study of OPT formulation was investigated in male Wistar rats, and in-vitro/in-vivo correlation level was established. Intestinal permeability of OPT formulation was determined using in situ single pass perfusion (SPIP) technique. Transmission electron microscopy studies on OPT formulation demonstrated uniform shape and size of particles. Augmentation in the values of K a (2.35-fold) and AUC 0-24 (2.91-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug. Successful establishment of in vitro/in vivo correlation (IVIVC) Level A substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. In situ SPIP studies ascribed the significant enhancement in absorptivity and permeability parameters of OPT formulation transport through the Peyer's patches. The studies, therefore, indicate the successful formulation development of NPs with distinctly improved bioavailability potential and can be used as drug carrier for sustained or prolonged drug release. KeywordsBioavailability, central composite design, nanoparticles, pharmacokinetic study, in situ single pass perfusion studies, in vitro/in vivo correlation History

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P-glycoprotein limits the absorption of the anti-HIV drug zidovudine through rat intestinal segments

Cited by 28 publications

References 41 publications

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

A novel approach in mucoadhesive drug delivery system to improve zidovudine intestinal permeability

A Minireview: Usefulness of Transporter-Targeted Prodrugs in Enhancing Membrane Permeability

Atazanavir-loaded Eudragit RL 100 nanoparticles to improve oral bioavailability: optimization andin vitro/in vivoappraisal

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