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Polentarutti, Britta; Peterson, Anders; Sjöberg, Åsa; Anderberg, Eva Karin; Utter, L.; Ungell, Anna‐Lena

doi:10.1023/a:1018890106045

Cited by 82 publications

(26 citation statements)

References 22 publications

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“…Furthermore, for everted sac preparations the time required from dissection up to and including preparation should not exceed 8 min [103] and the tissue should be kept in the oxygenated buffer solution continuously [103]. Also the intactness of Ussing chamber preparations, which can be demonstrated by the stability of electrical parameters in this system is dependent on the overall 'prechamber' treatment, from the anesthesia of the rats to the mounting of the tissue and the rat tissue should be kept in constantly oxygenated KBR solution directly after excision [104]. Surprisingly, preparations of human, pig, rabbit and chicken intestine survive much longer than those of rodents (rat, mouse).…”

Section: In Vitro Methods To Study Drug Metabolismmentioning

confidence: 99%

“…The equipment is commercially available but custom made equipment is also used. The amount of tissue necessary for one set-up ranges from 3.8 mm 2 [125] -5 mm 2 [126] in the smaller version, to 0.65-1.78 cm 2 in the larger version [104,123,[127][128][129]. The smallest chambers (mm 2 -range) have, up to now, only been used for absorption studies [125,126] and are very promising in the light of the scarce availability of human tissue.…”

Section: Ussing Chambermentioning

confidence: 99%

“…The chambers have been successfully used up to 90 min [130], 120 min [123,129], 180 min [19,84,104] and even to 8 h as reported by Lampen et al [131] who showed that the conductivity remains constant up to 8 h [131]. Polentarutti et al have validated their Ussing chamber preparations thoroughly and based on the potential difference (PD) (> 4mV small intestine; > 6mV colon), short circuit current (SCC), resistance, permeability for propranolol and mannitol as well as morphological evaluation they have concluded that tissue integrity is maintained up to 180 min [104]. Soderholm et al have included the permeability of 51 Cr-EDTA as viability parameter and have reported that this is unchanged up to 120 min.…”

Section: Ussing Chambermentioning

confidence: 99%

“…From the latter study, it can be concluded that the choice of viability parameter drastically influences the period that the tissue is considered 'viable'. In most other studies the PD and SCC have been used and these remain stable up to 120-240 min [19,68,104,132].…”

Section: Ussing Chambermentioning

confidence: 99%

“…Ussing chamber preparations are generally incubated under carbogen [123,131,132] with KRB buffer solutions at pH 7.4 [68,104,131] as incubation medium [19,68,104,123,129,131,132], Ussing chamber preparations have also been used at pH 5.5 (luminal side) and pH 7.4 (serosal side) [133] or pH 6.0 both sides [129]. The bidirectional supply of glutamine to the incubation medium has been shown beneficial for the viability of Ussing chamber preparations, as it helps to maintain rat enterocyte ATP content in this system [128].…”

Section: Ussing Chambermentioning

confidence: 99%

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In Vitro Methods to Study Intestinal Drug Metabolism

Kerkhof¹,

Graaf²,

Groothuis

2007

CDM

109

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Although the liver has long been thought to play the major role in drug metabolism, also the metabolic capacity of the intestine is more and more recognized. In vivo studies eventually pointed out not only the significance of first-pass metabolism by the intestinal wall for the bioavailability of several compounds, but also the relevance of transporters in this process. Only a few methods are available to study drug metabolism in vivo or in situ and with most of these methods it remains difficult to discriminate between the contribution of liver and extrahepatic tissues. To study intestinal drug metabolism in vitro, apart from subcellular fractions, several intact cell systems are nowadays available. This review discusses the available intestinal in vitro methods to study drug metabolism. The advantages and limitations of intact cell systems (isolated intestinal perfusion, everted sac, Ussing chamber preparations, biopsies, precision-cut slices, primary cells), subcellular fractions (S9 fractions, microsomes) and intestinal cell lines (caco-2, LS180 cells amongst others) are discussed. Their applicability to different species and to study phase I and II metabolism/transport and drug-drug interactions are summarized. Furthermore, causes of variation within and between methods are discussed and metabolic rates obtained with different methods are compared. Whereas subcellular fractions and cell lines are efficient methods to study mechanistic aspects of drug metabolism at the enzyme level, the isolated intestinal perfusion, everted sac and Ussing chamber appear particularly useful for studying drug metabolism of rapidly metabolised drugs and interactions with transporters. Biopsies, precision-cut slices and primary cells seem all appropriate to study induction and metabolism of slowly metabolised drugs.

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Section: In Vitro Methods To Study Drug Metabolismmentioning

confidence: 99%