In Situ Single-Pass Perfused Rat Intestinal Model for Absorption and Metabolism

Jeong, Eun Ju; Liu, Yan; Lin, Huimin; Hu, Ming

doi:10.1385/1-59259-800-5:065

Cited by 24 publications

(20 citation statements)

References 7 publications

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“…Data from Caco-2 cell and rat intestinal perfusion suggested that bicyclol is a well absorbed compound comparable to other well-absorbed markers (21).However, the high permeability did not lead to high-level of bicyclol in the mesenteric blood (23), indicating that p-gp mediated efflux and drug metabolizing enzyme may both contribute to the poor bioavailability of bicyclol. It was found that the permeability of bicyclol (P app A-B = 1.6±0.3×10 -5 cm/s) in Caco-2 cell was similar to those of well-absorbed compounds such as propranolol (1.13×10 -5 cm/s), and testosterone (3.3×10 -5 cm/s) (24). The result from rat perfusion was consistent with in vitro study (25).…”

Section: Disscusionsupporting

confidence: 81%

A study of intestinal absorption of bicyclol in rats: active efflux transport and metabolism as causes of its poor bioavailability

et al. 2008

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-Purpose. To determine the possible mechanism of poor bioavailability of bicyclol, and clarify the respective contribution of P-glycoprotein (P-gp) and Cytochrome 3A (CYP3A). Methods. Rat in situ single-pass intestinal perfusion and Caco-2 cell monolayer model with selective inhibitors of CYP3A and P-gp were employed. Results. In rat intestinal perfusion, bicyclol (50µM) appearance in mesenteric blood (P blood ) was increased 3, 12 and 16-fold after addition of inhibitors of P-gp (LSN335984), CYP3A (troleandomycin, TAO) or P-gp and CYP3A (Cyclosporin A, CsA), respectively, whereas permeability of midazolam (CYP3A substrate only) was unchanged after addition of LSN335984 and increased 5 fold after addition of TAO. Moreover, the cumulative amount of bicyclol in mesenteric blood was increased at concentration range 10-100µM of bicyclol in perfusate. The basolateral to apical permeability value of bicyclol in Caco-2 monolayer was significantly deceased by LSN335984 and CsA. Conclusions. The poor bioavailability of bicyclol is mostly due to P-gp mediated efflux and metabolism by CYP3A in intestine, with CYP3A making more contribution than P-gp.

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Section: Disscusionsupporting

confidence: 81%

A study of intestinal absorption of bicyclol in rats: active efflux transport and metabolism as causes of its poor bioavailability

et al. 2008

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“…Simultaneous perfusions, as described previously in rats (Jeong et al, 2004), were adapted for our studies in wild-type and Pept1 knockout mice. Before cannulations of different intestinal segments, the common bile duct was ligated by silk suture.…”

Section: Methodsmentioning

confidence: 99%

Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type andPept1Knockout Mice

Jappar¹,

Wu²,

Hu³

et al. 2010

Drug Metab Dispos

109

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“…Single-pass intestinal perfusion (SPIP) studies were performed according to the previously established methods (Jeong et al, 2004;Salphati et al, 2001;ZakeriMilani et al, 2007ZakeriMilani et al, , 2008ZakeriMilani et al, , 2009a. Briefly, male Wistar rats (250-300 g) were maintained on a 12 h light-dark cycle and fasted 12-18 h overnight before the experiment.…”

Section: Single-pass Intestinal Perfusion Experimentsmentioning

confidence: 99%

“…Caco-2 cells); uptake studies in brush-border membrane vesicles prepared from intestinal segments of various species; and the single-pass intestinal perfusion (SPIP) in small mammals, most commonly rats (Artursson, Karlsson, 1991;Hillgren et al, 1995;Salphati et al, 2001). Among these, single-pass intestinal perfusion (SPIP) provides conditions closer to what is faced following oral administration (Cook, Shenoy, 2003;Jeong et al, 2004). This technique has low sensitivity to pH variations due to the preserved microclimate above the epithelial cells, and it maintains an intact blood supply to the intestine as well as providing the unique advantages of experimental control (e.g.…”

Section: Introductionmentioning

confidence: 99%

A study on enhanced intestinal permeability of clarithromycin nanoparticles

Zakeri–Milani

Islambulchilar

Majidpour

et al. 2014

Braz. J. Pharm. Sci.

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The main objective of the present study was to determine the permeability of clarithromycin (CLA)-PLGA nanoparticles using single-pass intestinal perfusion technique in rats. Clarithromycin nanoparticles were prepared by nano-precipitation according to the modified quasi emulsion solvent diffusion technique and evaluated for their physicochemical characteristics. Permeability coefficients (P eff ) in anaesthetized rats were determined at 3 different concentrations. Drug solution or suspensions in PBS was perfused through a cannulated jejunal segment and samples were taken from outlet tubing at different time points up to 90 min. Microbiological assay of CLA and phenol red in the samples were analyzed using an agar well diffusion procedure and HPLC method respectively. The average particle size of prepared nanoparticles was 305 ± 134 nm. The mean P eff of CLA solution in concentrations of 150, 250 and 400 µg/mL was found to be 1.20 (±0.32) ×10 -3 , 9.62 (±0.46) ×10 -4 , and 1.36 (±0.95) ×10 -3 cm/sec, respectively. The corresponding values for the same concentration of nanoparticles were found to be 2.74 (±0.73) ×10 -3 , 2.45 (±0.88) ×10 -3 , and 3.68 (±0.46) ×10 -3 cm/s, respectively. The two-tailed Student's t-test showed that the intestinal permeability of CLA nanoparticle suspensions in prepared concentrations were significantly increased in comparison with its solution.Uniterms: Clarithromycin/nanoparticles/ permeability. Single-Pass Intestinal Perfusion. Intestinal permeability.O objetivo principal do presente estudo foi determinar a permeabilidade de nanopartículas de claritromicina (CLA)-PLGA, utilizando a técnica de perfusão intestinal de passo único em ratos. As nanopartículas de claritromicina foram preparadas por nanoprecipitação, de acordo com a técnica modificada de difusão de solvente quase-emulsão, e suas características físico-químicas avaliadas. Os coeficientes de permeabilidade (P eff ) em ratos anestesiados foram determinados em três concentrações diferentes. A solução, ou suspensões, do fármaco em PBS foi perfundida através do segmento de jejuno canulado e as amostras foram tomadas do tubo externo em diferentes tempos até 90 minutos. Os ensaios microbiológico de CLA e de vermelho de fenol das amostras foram realizados, utilizando-se o procedimento de difusão em poço de ágar e de CLAE, respectivamente. O tamanho médio das partículas das nanopartículas preparadas foi de 305 ± 134 nm. O P eff médio da solução de CLA em concentrações de 150, 250 and 400 µg/mL foi de 1.20(±0.32)×10 -3 , 9.62(±0. INTRODUCTIONOral administration remains the most convenient and useful route for delivering most pharmaceutical agents. However, the major problem of many orally administered drugs is to overcome several barriers before reaching their target site (Cook, Shenoy, 2003;Rao et al., 2008). Several approaches have been applied in order to improve the oral bioavailability of poorly permeable and soluble compounds intended for oral administration. Using nanoparticulate drug delivery system is considered as one of...

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In Situ Single-Pass Perfused Rat Intestinal Model for Absorption and Metabolism

Cited by 24 publications

References 7 publications

A study of intestinal absorption of bicyclol in rats: active efflux transport and metabolism as causes of its poor bioavailability

A study of intestinal absorption of bicyclol in rats: active efflux transport and metabolism as causes of its poor bioavailability

Significance and Regional Dependency of Peptide Transporter (PEPT) 1 in the Intestinal Permeability of Glycylsarcosine: In Situ Single-Pass Perfusion Studies in Wild-Type andPept1Knockout Mice

A study on enhanced intestinal permeability of clarithromycin nanoparticles

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