Publications by authors named "Eva M Karlsson"
Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns.
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- Assessing drug-drug interactions (DDIs) for weakly acidic compounds can enhance patient safety and inform pharmaceutical practices, especially when examining the effects of acid-reducing agents (ARAs) on drug solubility.
- The study investigated the dissolution behavior of potassium raltegravir tablets in biorelevant conditions to simulate both ARA co-administration and typical gastric environments, using data for in silico modeling with Simcyp™.
- Results indicated that dissolution in ARA-simulated conditions was quicker and more complete than in low pH conditions, suggesting this method could effectively predict drug behavior during combined therapy and may apply to other similar drugs.
Article Synopsis
- In vitro and in silico techniques are crucial for evaluating metabolic drug-drug interactions (DDIs), particularly the effects of acid-reducing agents (ARAs) on the pharmacokinetics of poorly soluble basic drugs.
- Dipyridamole dissolution testing with biorelevant media showed that existing in vitro methods might overestimate drug precipitation in the intestines, prompting the use of one-stage dissolution testing and PBPK modeling for better accuracy.
- Results indicated that the combination of dissolution methods and PBPK modeling effectively simulated ARA-related interactions with dipyridamole, and that the TIM-1 system could also forecast these effects when adjusted for gastric pH changes.
Background: Oral medicines must release the drug appropriately in the GI tract in order to assure adequate and reproducible absorption. Disease states and co-administration of drugs may alter GI physiology and therefore the release profile of the drug. Acid-reducing agents (ARAs), especially proton pump inhibitors (PPIs), are frequently co-administered during various therapies.
View Article and Find Full Text PDFBackground: Of the various drug therapies that influence gastrointestinal (GI) physiology, one of the most important are the acid-reducing agents (ARAs). Because changes in GI physiology often influence the pharmacokinetics of drugs given orally, there is a need to identify in vitro methods with which such effects can be elucidated.
Objective: Literature concerning the effects of ARAs (antacids, H-receptor antagonists, and proton pump inhibitors [PPIs]) on GI physiology are reviewed with the aim of identifying conditions under which drugs are released after oral administration in the fasted state.
The high number of poorly water-soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g.
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