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Kathy Sweeney - One of the best experts on this subject based on the ideXlab platform.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical Research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    Purpose This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. Methods The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. Results Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability ∼ low solubility, low permeability. Conclusion The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    PURPOSE This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. METHODS The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. RESULTS Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability approximately low solubility, low permeability. CONCLUSION The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

Steven C. Sutton - One of the best experts on this subject based on the ideXlab platform.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical Research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    Purpose This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. Methods The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. Results Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability ∼ low solubility, low permeability. Conclusion The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    PURPOSE This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. METHODS The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. RESULTS Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability approximately low solubility, low permeability. CONCLUSION The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

  • A computational model for particle size influence on drug Absorption during controlled-release Colonic delivery.
    Journal of controlled release : official journal of the Controlled Release Society, 2003
    Co-Authors: Kenneth C Waterman, Steven C. Sutton
    Abstract:

    The effect of particle size on the percent drug absorbed is computationally modeled for controlled-release dosage forms that deliver drug particles to the Colon. The relative benefit of reducing particle size is mapped on a diagram of the drug's Absorption rate constant (estimated from rat intestinal perfusion, CACO-2 or human intubation permeation rates) versus the drug's solubility. Some drugs fall into a limit of high percentage Absorption even with large particles such that particle size reduction has little impact. Another group of drugs is solubility limited such that even with small particles, Absorption is negligible. Between the two regions, only drugs with sufficiently high Absorption rates are influenced by the drug dissolution rate and thereby the particle size. The size of this region is a function of dosing rate. Comparisons between calculated particle size effects on Colon Absorption as a function of Colon volume suggest caution when using animal models to predict bioavailability from Colonic drug delivery. This volume dependence also suggests that the particle size influence will vary as a function of the digestive cycle.

A. H. Staib - One of the best experts on this subject based on the ideXlab platform.

  • Investigation of nifedipine Absorption in different regions of the human gastrointestinal (GI) tract after simultaneous administration of 13C- and 12C-nifedipine
    European Journal of Clinical Pharmacology, 1996
    Co-Authors: H. Bode, E. Brendel, G. Ahr, U. Fuhr, S. Harder, A. H. Staib
    Abstract:

    Objective : To evaluate the Absorption of nifedipine in man from four different sites of the gastrointestinal tract. Methods: On separate occasions, nifedipine solution was administered locally to the stomach, the small intestine and two sites in the Colon in 4 healthy male volunteers (age 29–34 y weight 73–82 kg, non-smokers) using a remote controlled drug delivery device (HF-capsule). In order to assess absolute and relative bioavailabilities, an intravenous infusion was given on a separate occasion and all treatments were accompanied by a simultaneous oral dose of a stable-isotope labelled nifedipine solution. This allowed to minimise the influence of intra-individual variability. Plasma samples were collected up to 24 h post dose and faeces for 72 h. A new method of analysis of nifedipine in plasma and faeces using gas chromatography with mass-selective detection (GCMS) was employed. Results: Dissolved nifedipine was found to enter the systemic circulation completely along the intestine, being absorbed from jejunum to Colon. Absorption was less rapid from the Colon than from the upper part of the gut, but this was not associated with a decrease in Absorption and/or bioavailability: Absolute bioavailability, calculated from the normalised AUC values, ranged from 42 to 56%, and bioavailability relative to oral solution was 100 to 126% (medians of the application sites). Conclusion: The absence of an Absorption window in the intestinal tract suggests that nifedipine is well suited for use in controlled-release formulations.

Jennifer M. Mccarthy - One of the best experts on this subject based on the ideXlab platform.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical Research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    Purpose This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. Methods The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. Results Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability ∼ low solubility, low permeability. Conclusion The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    PURPOSE This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. METHODS The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. RESULTS Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability approximately low solubility, low permeability. CONCLUSION The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

Jay H. Fortner - One of the best experts on this subject based on the ideXlab platform.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical Research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    Purpose This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. Methods The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. Results Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability ∼ low solubility, low permeability. Conclusion The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.

  • Dog Colonoscopy Model for Predicting Human Colon Absorption
    Pharmaceutical research, 2006
    Co-Authors: Steven C. Sutton, Loreen A. Evans, Jay H. Fortner, Jennifer M. Mccarthy, Kathy Sweeney
    Abstract:

    PURPOSE This study was conducted to develop and validate a dog Colon model that predicts Colon permeability in humans. METHODS The following compounds were studied: Class 1 highly soluble (HS)/highly permeable (HP): aminophylline, propranolol, CP-409092; Class 2 LS/HP: nifedipine; trovafloxacin, sertraline; Class 3 HS/LP: azithromycin, atenolol, CP-331684, CP-424391; Class 4 LS/LP: CJ-13610. Administration to dogs was made 30 cm cranial to the anal sphincter with a lubricated Schott Model VFS-5 flexible endoscope. The bioavailability of the compound following the Colon administration in dogs, relative to the same formulation administered orally (relative bioavailability), was determined. RESULTS Except for atenolol, a small hydrophillic molecule, the relative bioavailability from administration to the Colon of the dog correlated well with the following compound properties: high solubility and high, passive permeability > high solubility, low permeability > low solubility, high, passive permeability approximately low solubility, low permeability. CONCLUSION The dog Colon model is proposed as a surrogate for human intubation studies when the controlled release candidate falls in BCS Classes 2 (LS/HP), 3 (HS/LP), and 4 (LS/LP). However, no human intubation or dog Colon studies are required for Class 1 (HS/HP), as these compounds are likely to be well absorbed from the Colon.