Drug Absorption from Large Intestine: Physicochemical Factors Governing Drug Absorption.

Kimura, Toshikiro; Sudo, Kenji; Kanzaki, Yasuhiro; Miki, Kazumi; Takeichi, Yoichiro; Kurosaki, Yuji; Nakayama, Taiji

doi:10.1248/bpb.17.327

Cited by 47 publications

(18 citation statements)

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“…In no instances were these mixed populations of virus found in the plasma in the absence of mixtures in the other compartments. It is plausible that the intestine is less readily permeated by antiviral medications [14] or metabolically inactivates these medications [15] to a greater degree than plasma, which leads to lower effective drug levels and retention of replicating strains of virus with a wild-type genotype. Again, the presence of mixed virus populations in the PBMC may reflect redistribution from the mucosa or vice versa.…”

Section: Discussionmentioning

confidence: 99%

Despite High Concordance, Distinct Mutational and Phenotypic Drug Resistance Profiles in Human Immunodeficiency Virus Type 1 RNA Are Observed in Gastrointestinal Mucosal Biopsy Specimens and Peripheral Blood Mononuclear Cells Compared with Plasma

Poles

Elliott

Vingerhoets³

et al. 2001

J INFECT DIS

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The gastrointestinal mucosa is a major lymphoid tissue reservoir for human immunodeficiency virus (HIV) replication. Genotypic and phenotypic resistance patterns of HIV type 1 (HIV-1) RNA isolated from colonic mucosa were compared with those from the plasma and peripheral blood mononuclear cells (PBMC) of 7 patients. Genotyping was performed using full-sequence analysis, and phenotyping was performed using a recombinant virus assay. Mutations in the reverse-transcriptase (kappa=.84) and protease (kappa=.73) genes were highly concordant among compartments. Similarly, phenotypic resistance patterns were highly concordant among compartments (intraclass correlation coefficient,.91). In 5 instances among 3 patients, a different genotypic result was observed between plasma and the other tissue compartments. Mixtures of wild-type and mutated HIV-1 RNA were present in the mucosa and PBMC but not in the plasma. Despite significant concordance among compartments, mucosal- and PBMC-derived viral RNA showed instances of discordance with plasma-derived virus that may suggest compartmentalization of virus.

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Section: Discussionmentioning

confidence: 99%

Despite High Concordance, Distinct Mutational and Phenotypic Drug Resistance Profiles in Human Immunodeficiency Virus Type 1 RNA Are Observed in Gastrointestinal Mucosal Biopsy Specimens and Peripheral Blood Mononuclear Cells Compared with Plasma

Poles

Elliott

Vingerhoets³

et al. 2001

J INFECT DIS

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“…from methyl-to npentyl-) is in accordance with the result of other authors. Studying absorption in situ in rat jejunum, ileum, colon and rectum, Kimura et al [19] observed that at any of these sites, the absorption rates of a homologous series of salicylic acid esters increased with increasing acyl chain length (acetyl-, propionyl-and butyryl-). Houston et al [49] reported on the same trend for a homologous series of carbamates in rat tissue using an everted gut technique.…”

Section: Transport Studiesmentioning

confidence: 99%

“…the rate limiting step shifts from membrane-controlled to unstirred water layer-controlled permeability [16][17][18]. By studying acetyl-, propionyl-and butyrylsalicyclic acid, Kimura et al [19] reported an increase in permeability with increasing acyl chain length.…”

Section: Introductionmentioning

confidence: 99%

Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters

Werdenberg¹,

Joshi

Wolffram

et al. 2003

Biopharm & Drug Disp

113

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Psoriasis is a chronic inflammatory skin disease. Its treatment is based on the inhibition of proliferation of epidermal cells and interference in the inflammatory process. A new systemic antipsoriasis drug, which consists of dimethylfumarate and ethylhydrogenfumarate in the form of their calcium, magnesium and zinc salts has been introduced in Europe with successful results. In the present study, a homologous series of mono- and diesters of fumaric acid has been studied with respect to the sites and kinetics of presystemic ester degradation using pancreas extract, intestinal perfusate, intestinal homogenate and liver S9 fraction. In addition, intestinal permeability has been determined using isolated intestinal mucosa as well as Caco-2 cell monolayers, in order to obtain estimates of the fraction of the dose absorbed for these compounds. Relationships between the physicochemical properties of the fumaric acid esters and their biological responses were investigated. The uncharged diester dimethylfumarate displayed a high presystemic metabolic lability in all metabolism models. It also showed the highest permeability in the Caco-2 cell model. However, in permeation experiments with intestinal mucosa in Ussing-type chambers, no undegraded DMF was found on the receiver side, indicating complete metabolism in the intestinal tissue. The intestinal permeability of the monoesters methyl hydrogen fumarate, ethyl hydrogen fumarate, n-propylhydrogen fumarate and n-pentyl hydrogen fumarate increased with an increase in their lipophilicity, however, their presystemic metabolism rates likewise increased with increasing ester chain length. It is concluded that for fumarates, an increase in intestinal permeability of the more lipophilic derivatives is counterbalanced by an increase in first-pass extraction.

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“…Therefore, colon-specific drug delivery systems, which can deliver drugs to the lower gastrointestinal tract without releasing them in the upper GI tract, can be expected to decrease the side-effects of the drugs and improve the quality of life for patients suffering from colon-specific diseases (Fujino et al 1995). Generally, the colon is not as suitable site for drug absorption as is the small intestine, because the water content in the colon is much lower and the colonic surface area for drug absorption is narrow in comparison with the small intestine (Kimura et al 1994;Edwards 1996). However, the colon is a preferable site for the absorption of liable compounds such as peptides and proteins, because the hydrolytic enzyme activities of the colon are lower than that of the small intestine (Langguth et al 1997;Rubinstein et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Colon-specific drug delivery for mebeverine hydrochloride

Omar

Aldosari

Refai

et al. 2007

Journal of Drug Targeting

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Mebeverine Hydrochloride (MB-HCl), an effective spasmolytic drug, was formulated as CODES. A colon-specific drug delivery technology CODES was designed to avoid the inherent problems associated with pH- or time-dependent systems. To achieve more protection and control of drug release, MB-HCl was prepared as microspheres and compressed as core tablets of CODES (modified CODES). The core tablets contained the drug either in free form [Formula 1 (F(1))], or as microspheres with 2 different polymer:drug:lactulose ratios (1:1:0.5 [Formula 2 (F(2))] and 2:1:0.5 [Formula 3 (F(3))]. The release profiles of the coated CODES systems were compared with uncoated compressed tablets. The uncoated tablet showed a drug release of 94% after 1 h in simulated gastric condition (pH = 1.2). The release characteristics of the coated systems revealed that the enteric coating (Eudragit L(100)) prevented any drug release in simulated gastric or duodenal conditions in the first 3 h (pH 1.2-6.1), after which drug was slightly liberated in simulated intestinal fluid (pH 7.4) {Phase 1 (P1)}. After 4 h the pH was adjusted to 7 and beta-glucose-oxidase was added, which is an enzyme produced by enterobacteria present in the colon. The acid-soluble coat (Eudragit)E(100)) dissolved and the drug release suddenly increased to reach 95, 72 and 60.4% for F(1)-F(3), respectively. IR spectrum study showed a covalent bond between the drug and the polymer in the formulae F(2) and F(3) resulting in the sustained drug release from the microspheres with a significant difference (p>0.05) to F(1). The findings were confirmed by in vivo investigation using X-ray images for Guinea pigs ingested tablets containing barium sulphate (F(4)), where the tablet began to disintegrate after 10 h of tablet intake. The results of the study indicated that MB-HCl CODES colon-specific drug delivery can act as a successful trigger for drug targeting in the colon. Furthermore, a sustained release of the drug can be achieved from modified CODES containing the drug in the form of microspheres.

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Drug Absorption from Large Intestine: Physicochemical Factors Governing Drug Absorption.

Cited by 47 publications

References 0 publications

Despite High Concordance, Distinct Mutational and Phenotypic Drug Resistance Profiles in Human Immunodeficiency Virus Type 1 RNA Are Observed in Gastrointestinal Mucosal Biopsy Specimens and Peripheral Blood Mononuclear Cells Compared with Plasma

Despite High Concordance, Distinct Mutational and Phenotypic Drug Resistance Profiles in Human Immunodeficiency Virus Type 1 RNA Are Observed in Gastrointestinal Mucosal Biopsy Specimens and Peripheral Blood Mononuclear Cells Compared with Plasma

Presystemic metabolism and intestinal absorption of antipsoriatic fumaric acid esters

Colon-specific drug delivery for mebeverine hydrochloride

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