Effect of Bile Salts on the Gastrointestinal Absorption of Drugs. II. Mechanism of the Enhancement of the Intestinal Absorption of Sulfaguanidine by Bile Salts

Kakemi, Kiichiro; Sezaki, Hitoshi; Konishi, Ryoji; Kimura, Takeshi; A, Okita

doi:10.1248/cpb.18.1034

Cited by 49 publications

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“…2 (GITA Model 12) ). The absorption rate constant (ka i ) for each segment was determined by a conventional in-situ closed loop method 19,20) and the GI transit rate constant (k i ) for each seg- The gastrointestinal (GI) absorption of orally administered drugs is determined by not only the permeability of GI mucosa but also the transit rate in the GI tract. It is well known that the gastric emptying rate is an important factor affecting the plasma concentration profile of orally administered drugs, and the intestinal transit rate also has a significant influence on the drug absorption, since it determines the residence time of the drug in the absorption site.…”

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Gastrointestinal Transit and Drug Absorption

Kimura

Higaki

2002

Biological & Pharmaceutical Bulletin

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173

114

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Oral drug administration is the most convenient and common for drug therapy and it is, therefore, very important and useful to estimate the absorbability of drugs and to predict the plasma concentration profile of drugs after oral administration for the development of novel drugs and/or novel dosage form and the designation of the dosage regimen. Generally, the absorbability of drugs has been estimated by in-situ recirculation studies, in-situ closed loop studies or the analysis by the simple compartment model. The information which can be obtained from these approaches is usually an absorption rate constant, ka. The ka value is generally the averaged one throughout the intestinal tract. However, there is the site-difference in drug absorbability [1][2][3][4] and variable residence time of drugs in each segment must make the contribution of each segment to drug absorption changed, resulting in the different absorbability as a whole. As for the drug absorption after oral administration, the gastrointestinal (GI) transit of a drug is also an important factor to determine the drug absorption and is so variable, as was influenced by not only individual differences, 5) but also the dosage conditions like meals, 6) disease states 7) and so on. Therefore, the absorbability and the residence time in each segment are the major determining factors for drug absorption after oral administration and very important for the analysis of drug absorption kinetics and the estimation of, and the prediction of plasma concentration profiles of drugs. However, the analysis and the estimation of drug absorption after oral administration have been usually performed by a simple compartment model, where even a process of gastric emptying is not included often. This kind of simple model cannot describe the irregular shape in the plasma concentration, which is often observed. Therefore, several models were proposed to analyze the plasma profile, [8][9][10][11] but they are not necessarily based on the practical phenomena, i.e. GI transit and site-different drug absorbability.We have developed a GI-Transit-Absorption (GITA) Model containing the GI transit and absorption processes to analyze and predict the plasma concentration profile after oral administration of aqueous drug solution.12) Although several efficient methods to estimate the absorption of orally administered drug by analyzing the GI disposition following oral administration (GI disposition analysis) have been reported, some are only focused on the gastric emptying based on a model having a stomach and an intestine compartment. 13,14) The other one estimated the intestinal transit of a drug using polyethylene glycol 4000 as a nonabsorbable marker, 10) but the actual data of intestinal transit were not utilized enough to analyze and predict the drug absorption kinetics. Although the analytical procedures for plasma profile of a drug absorbed from successive absorption sites along the GI tract have been also reported, [16][17][18] they just showed the concept and/or simulation stu...

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Gastrointestinal Transit and Drug Absorption

Kimura

Higaki

2002

Biological & Pharmaceutical Bulletin

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173

114

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“…Xian et al (1995) reported that casein can protect IGF-I from degradation in the stomach or duodenal flushing, but the mechanisms of this protection are not clear. The inhibitory effect of HP-␤-CD and SDCh are relatively weak compared with bacitracin and casein, although some studies suggested that DM-␤-CD and SDCh have the ability of inhibiting the enzyme activities (Kakemi et al, 1970;Hovgaard and Brondsted, 1995). Regardless, it seems possible to use some protease inhibitors to IrHV2 alone or with adjuvant in rats, determined by TCA-precipitable method.…”

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Gastrointestinal Absorption of Recombinant Hirudin-2 in Rats

Yan¹,

Wang²,

Xue-nong³

et al. 2003

J Pharmacol Exp Ther

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“…The absorption experiments were performed in cecum using an in-situ closed loop method (18,19). Initial concentration of 9-AC was 72.9 μM.…”

Section: Determination Of Absorption Rate Constantmentioning

confidence: 99%

“…A closed loop method was used in the in-situ cecum absorption study to estimate the availability of 9-AC through the cecum and liver (F c,h ) after absorption from the cecum (18,19,21). The blood samples were collected from the right femoral artery after 72.9 μM of 9-AC in 4 ml of isotonic phosphate-buffered solution (pH 6.8) was administrated into the rat cecum.…”

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confidence: 99%

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

et al. 2007

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Purpose-To quantitate and predict colon-specific 9-aminocamptothecin (9-AC) release from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-9-AC conjugate and its absorption behavior after oral administration in rats.Methods-Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum. The fate of 9-AC in cecum and liver was measured by in-situ cecum absorption and liver perfusion.Results-Following oral administration of the conjugate, 9-AC was released rapidly in cecum. Based on the pharmacokinetic model, up to 60% of the dose was in the cecum at ∼6 h, and 7% of the dose still remained there at 24 h. The predicted plasma concentration curve for released 9-AC after an oral dose of 3 mg/kg of 9-AC equivalent increased gradually and reached a peak of 98 nM at 7 h, then started decreasing slowly to 16 nM at 24 h. The bioavailability value was estimated as 0.31 after the first-pass elimination.Conclusions-A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer-9-AC conjugate in rats.

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Effect of Bile Salts on the Gastrointestinal Absorption of Drugs. II. Mechanism of the Enhancement of the Intestinal Absorption of Sulfaguanidine by Bile Salts

Cited by 49 publications

References 0 publications

Gastrointestinal Transit and Drug Absorption

Gastrointestinal Transit and Drug Absorption

Gastrointestinal Absorption of Recombinant Hirudin-2 in Rats

Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

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