The effects of mucus glycoproteins on the bioavailability of tetracycline. III. Everted gut studies

Kearney, P.; Marriott, Christopher

doi:10.1016/0378-5173(87)90116-5

Cited by 13 publications

(2 citation statements)

References 23 publications

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“…Some drugs have been shown to chemically interact with the glycoproteins from mucus, limiting the drug absorption rate and decreasing drug bioavailability. These mucus–drug interactions can occur by electrostatic interactions between positively charged drugs and negatively mucins, which are ionized at pH > 2.6 (due to the sialic acid component), by hydrophobic interactions with the protein core of mucins or through hydrogen bonding [19–22] …”

Section: Introductionmentioning

confidence: 99%

Mucus thickness in the gastrointestinal tract of laboratory animals

Varum

Veiga

Sousa

et al. 2012

Journal of Pharmacy and Pharmacology

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Section: Introductionmentioning

confidence: 99%

Mucus thickness in the gastrointestinal tract of laboratory animals

Varum

Veiga

Sousa

et al. 2012

Journal of Pharmacy and Pharmacology

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“…The influence of the mucus layer on drug absorption has been investigated in in vivo studies of intestinal perfusion, 3 in vitro everted gut studies, 4 and diffusion studies in twocompartment or two-phase models 5,6 or three-compartment models. 5,7,8 These studies confirmed that mucus is a barrier to the diffusion and/or absorption of drug molecules.…”

Section: Introductionmentioning

confidence: 99%

Diffusion of Drugs in Native and Purified Gastrointestinal Mucus

Larhed¹,

Artursson²,

Gråsjö³

et al. 1997

Journal of Pharmaceutical Sciences

171

101

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The mucus layer covering the surface of the gastrointestinal tract may act as a barrier to drug absorption. The aim of this investigation was to study the self-diffusion coefficients of model drugs with different physicochemical properties in gastrointestinal mucus. An in vitro method was used to determine the self-diffusion coefficients of radiolabeled model drugs in different diffusion media. Glucosamine, mannitol, glucuronic acid, glucose, metoprotol, antipyrine, propranolol, hydrocortisone, and testosterone, which display large differences in charge and octanol/water distribution ratios (K), were used as model drugs. The diffusion coefficients of model drugs were compared in phosphate buffer (PB), native pig intestinal mucus (PIM), and purified pig gastric much (PPGM). PIM was not purified and therefore contained all the original components of native mucus, whereas PPGM contained only high molecular weight mucin molecules. Charge had only minor effects on the diffusion coefficients of the model drugs. Lipophilicity, however, had a much larger effect, the largest decrease in diffusion coefficient, 58%, was observed for testosterone in PIM. A negative relationship between the diffusion coefficient and log K was observed in PIM, but no relationship was observed in PPGM and PB. In contrast, the diffusion coefficients for two larger molecules of comparable size, the lipophilic peptide cyclosporin and the hydrophilic peptide D-arginine vasopressin, were markedly reduced in PIM. In conclusion, the most important physicochemical characteristic influencing the diffusion coefficient of most drugs in gastrointestinal mucus appears to be lipophilicity, whereas molecular size appears to have more influence for larger peptide drugs.

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