P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs

Aungst, Bruce J.

doi:10.1016/s0169-409x(99)00022-8

Cited by 76 publications

(53 citation statements)

References 60 publications

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“…This acid instability explains the low and highly variable bioavailability of ddI (20-40%) in comparison with others nucleoside reverse transcriptase inhibitors. Also, the first-pass metabolism of ddI is related to its low bioavailability (Aungst, 1999;Morse, Shelton, O'Donnell, 1993).…”

Section: Equilibrium Solubility and Biopharmaceutics Classificationmentioning

confidence: 99%

“…However, even formulations containing excipients used for buffering the gastrointestinal content are not completely capable to avoid ddI degradation, which may limit its bioavailability (Aungst, 1999). Thus, the relationship pH-solubility is extremely important for ddI, which has its permeability and bioavailability hindered by solubility conditions.…”

Section: Equilibrium Solubility and Biopharmaceutics Classificationmentioning

confidence: 99%

“…Thus, solubility characterization of this antiretroviral drug allows researchers to understand if these parameters can disturb the drug's bioavailability. Despite its low metabolism, didanosine presents low fraction absorbed (25-43%) (Aungst, 1999;Li, Chan, 1999;Moyer et al, 1999;Tavelin et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

Dezani

Ferreira

et al. 2017

Braz. J. Pharm. Sci.

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BCS (Biopharmaceutics Classification System) and BDDCS (Biopharmaceutics Drug DispositionClassification System) were proposed as tools for classifying drugs into four categories. Both systems consider the solubility as an important characteristic for the classification of compounds in drug development and in vivo disposition prediction. Although some results of drug solubility can be found in the literature, the aforementioned characteristic is not entirely clear when considering didanosine (ddI). Based on that, the solubility of ddI was evaluated using equilibrium and intrinsic dissolution methods. For the equilibrium method, excess amount of ddI was added to each media until obtaining a supersaturated solution and the mixture was submitted to agitation at 37 °C. For the intrinsic dissolution method, the drug was compressed into the Wood's apparatus matrix and subjected to dissolution in each media with agitation at 37 °C. The results obtained from the equilibrium method indicated that it was necessary 139.37 mL of pH 1.2 media, 87.72 mL of pH 4.5 media, 12.54 mL of pH 6.8 media, 5.03 mL of pH 7.5 media and 7.65 mL of purified water for drug solubilization. Furthermore, a very fast intrinsic dissolution rate (IDR) was obtained for each media: 0.1 mg/min/cm² (pH 1.2), 0.2 mg/min/cm² (pH 4.5), 0.2 mg/ min/cm² (pH 6.8), 0.1 mg/min/cm² (pH 7.5) and 0.1 mg/min/cm² (purified water). Based on these results, ddI can be considered as a highly soluble drug for both equilibrium and intrinsic dissolution methods.

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Section: Equilibrium Solubility and Biopharmaceutics Classificationmentioning

confidence: 99%

Section: Equilibrium Solubility and Biopharmaceutics Classificationmentioning

confidence: 99%

See 1 more Smart Citation

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

Dezani

Ferreira

et al. 2017

Braz. J. Pharm. Sci.

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“…It shows pH-dependent solubility and solution stability [15]. Moreover, it is primarily absorbed from stomach [16] and having short half-life (~3-5 hrs). Due to these characteristics, it was selected for the development of GRDDS.…”

Section: Introductionmentioning

confidence: 99%

Development and Characterization of Gastroretentive Drug Delivery System for Ritonavir Tablets Using Natural Polymers

Chukka

Shaik

2017

Asian J Pharm Clin Res

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Objective: This study involves preparation and evaluation of floating tablets of ritonavir (RN) for improving the drug bioavailability by prolongation of gastric residence time. RN is an antiretroviral agent used in the treatment of HIV and viral diseases have been taken as a model drug in this investigation because of its low biological half-life (3-5 hrs). Moreover, it is primarily absorbed from stomach.Methods: RN floating tablets were prepared by the dry granulation technique, using guar gum and xanthan gum as polymers, sodium bicarbonate as effervescent agent, polyvinylpyrrolidone as binding agent, Dicalcium phosphate as diluents, crospovidone as swelling agent and magnesium stearate as lubricant. The prepared tablets were evaluated for various physicochemical parameters.Results: Drug-excipient interaction studies were conducted by Fourier transform infrared spectroscopy and differential scanning calorimetry. The results suggested that there was no incompatibility between the drug and polymers. The prepared tablets were evaluated for their physical characteristics. All the parameters were within the pharmacopoeial limits. Further, tablets were also studied for their floating properties and in vitro drug release characteristics. The tablets exhibited controlled and prolonged drug release profiles. The developed formulation was found to be stable. Conclusion:The developed floating tablets of RN exhibit prolonged release up to 12 hrs, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations.

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“…Furthermore, drug exposure in hepatocytes may also be limited by the various unidirectional active transport (ATP dependent) proteins, including P-gp, BCRP\ABCG2, and MRP2 (Castell et al 2006;Chandra and Brouwer 2004;Elferink and Groen 2002;Gomez-Lechon et al 2004;Leslie et al 2005;Pauli-Magnus and Meier 2006;Vermeir et al 2005). Although nucleoside analogs are not substrates for P-gp or CYP3A4, most protease inhibitors and NNI are substrates for both the P-gp efflux pump (Aungst 1999;Storch et al 2007) and CYP3A 4 metabolism (Sagir et al 2003;Zhou et al 2005). The HIV protease inhibitors ritonavir and atazanavir are potent inhibitors of both P-gp and CYP3A4.…”

Section: Physiological Factors That Influence Drug Delivery For Hcv Dmentioning

confidence: 99%

Approaches for the Development of Antiviral Compounds: The Case of Hepatitis C Virus

Schinazi

Coats

Bassit

et al.

Antiviral Strategies

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P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs

Cited by 76 publications

References 60 publications

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

Solubility evaluation of didanosine: a comparison between the equilibrium method and intrinsic dissolution for biopharmaceutics classification purposes

Development and Characterization of Gastroretentive Drug Delivery System for Ritonavir Tablets Using Natural Polymers

Approaches for the Development of Antiviral Compounds: The Case of Hepatitis C Virus

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