WFRF:(Sigfridsson Kalle)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03568naa a2200397 4500 | |
| 001 | oai:research.chalmers.se:08a63a69-6cb4-496d-b0d7-b528ab2e19ee | |
| 003 | SwePub | |
| 008 | 171007s2011 | |||||||||||000 ||eng| | |
| 024 | 7 | a https://research.chalmers.se/publication/1928712 URI |
| 024 | 7 | a https://doi.org/10.3109/03639045.2011.5589022 DOI |
| 040 | a (SwePub)cth | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a art2 swepub-publicationtype |
| 072 | 7 | a ref2 swepub-contenttype |
| 100 | 1 | a Sigfridsson, Kalle,d 1964u Chalmers tekniska högskola,Chalmers University of Technology4 aut0 (Swepub:cth)carsig |
| 245 | 1 0 | a Co-administration of a nanosuspension of a poorly soluble basic compound and a solution of a proton pump inhibitor-the importance of gastrointestinal pH and solubility for the in vivo exposure |
| 264 | c 2011-03-21 | |
| 264 | 1 | b Informa UK Limited,c 2011 |
| 520 | a In Sigfridsson et al. (2011, Drug Dev Ind Pharm, 37: 243-251), there was no difference in plasma concentration of BA99 when administering the drug as nanosuspension or microsuspension and analyzing the blood samples by liquid chromatography-mass spectrometry. This was related to the dissolved amount of drug in the gastric tract, which was high enough to support fast absorption when the drug reached the small intestine. One single physicochemical property (pK(a), about 3 for BA99) abolished the benefit of small particles. These results were further confirmed in the present study, where a proton pump inhibitor, AZD0865, was used to elevate the gastric pH and then drastically decreased the gastric solubility. In this way, BA99 could be considered as a model compound for a neutral substance. By increasing the gastric pH to 5-6 and 8-9, respectively, in rats, the plasma concentrations of BA99, after administering nanosuspensions, were unchanged compared with untreated (i.e. no AZD0865) animals. For microsuspensions of the test compound, on the other hand, the exposure of BA99 was 2- to 3-fold lower than for nanosuspensions at both pHs. Moreover, the blood concentrations of BA99 administered as microsuspension were also 2- to 3-fold lower compared with untreated (no AZD0865) individuals receiving both nanoparticles and microparticles of BA99. Obviously, for neutral compounds, with similar physicochemical properties as the present compound, size reduction will be crucial for increased plasma exposure. For basic compounds, with similar physicochemical properties as the present compound, the crucial step for absorption is the dissolution and solubility in the gastric tract. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmakologi och toxikologi0 (SwePub)301022 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmacology and Toxicology0 (SwePub)301022 hsv//eng |
| 653 | a poorly soluble | |
| 653 | a Dissolution rate | |
| 653 | a gastric pH | |
| 653 | a suspension | |
| 653 | a pharmacokinetic | |
| 653 | a proton pump inhibitor | |
| 653 | a nanosuspension | |
| 700 | 1 | a Lundqvist, A.u AstraZeneca AB4 aut |
| 700 | 1 | a Strimfors, Marieu AstraZeneca AB4 aut |
| 710 | 2 | a Chalmers tekniska högskolab AstraZeneca AB4 org |
| 773 | 0 | t Drug Development and Industrial Pharmacyd : Informa UK Limitedg 37:9, s. 1036-1042q 37:9<1036-1042x 0363-9045x 1520-5762 |
| 856 | 4 | u http://dx.doi.org/10.3109/03639045.2011.558902y FULLTEXT |
| 856 | 4 8 | u https://research.chalmers.se/publication/192871 |
| 856 | 4 8 | u https://doi.org/10.3109/03639045.2011.558902 |
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