Enhancing Atorvastatin In Vivo Oral Bioavailability in the Presence of Inflammatory Bowel Disease and Irritable Bowel Syndrome Using Supercritical Fluid Technology Guided by wbPBPK Modeling in Rat and Human.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are common disorders that can change the body's physiology and drugs pharmacokinetics. Solid dispersion (SD) preparation using supercritical fluid technology (SFT) has many advantages. Our study aimed to explore the effect of IBS and IBD on atorvastatin (ATV) pharmacokinetics, enhance ATV oral bioavailability (BCS II drug) using SFT, and analyze drug-disease-formulation interaction using a whole-body physiologically based pharmacokinetic (wbPBPK) model in rat and human. A novel ATV formulation was prepared using SFT and characterized in vitro and in vivo in healthy, IBS, and IBD rats. The resulting ATV plasma levels were analyzed using a combination of conventional and wbPBPK approaches. The novel formulation increased ATV solubility by 20-fold and resulted in a zero-order release of up to 95%. Both IBS and IBD increased ATV exposure after oral and intravenous administration by more than 30%. The novel SFT formulation increased ATV bioavailability by 28, 14, and 18% in control, IBD, and IBD rat groups and resulted in more consistent exposure as compared to raw ATV solution. Higher improvements in ATV bioavailability of more than 2-fold upon receiving the novel SFT formulation were predicted by the human wbPBPK model as compared to receiving the conventional tablets. Finally, the established wbPBPK model could describe ATV ADME in the presence of IBS and IBD after oral administration of raw ATV and using the novel SFT formula and can help scale the optimized ATV dosing regimens in the presence of IBS and IBD from rats to humans.

Risk factors for duodenal ulcer disease.

OBJECTIVE: To evaluate the role played by some of the traditional risk factors on the prevalence of duodenal ulcer disease in Jordan, where the prevalence of Helicobacter pylori is high. METHODS: This study was carried out in the Endoscopy unit at the Health Center, Jordan University of Science and Technology, Irbid, Jordan, during the period January 1998 through to july 1999. The patients' group consisted of 290 subjects with endoscopically proven duodenal ulcers and 161 subjects who were endoscoped for various indications and found to have no ulcers were considered as controls. Validated questionnaires were filled out before the procedure, containing data related to age, sex, area of residence, family history of ulcer, blood grouping, cigarette smoking, coffee and tea ingestion, and regularity of meals. RESULTS: The following factors were associated with increased ulcer prevalence, male gender, family history of ulcer, blood group O, skipping breakfast or more than one meal, coffee ingestion and cigarette smoking. CONCLUSION: Many factors are important in the predisposition for ulcer disease in subjects with Helicobacter pylori. Modification of these factors would be essential to decrease the prevalence of ulcer disease and will result in large economic and medical savings.