Purpose: The study was designed to evaluate the effect of delayed release (DR) on absorption and bioavailability of intestinally metabolized drugs after oral dosing, using the HMG-CoA reductase inhibitor simvastatin, a CYP3A substrate, as a model drug.
Materials And Methods: To target drug release and to assess regional gastrointestinal absorption of the CYP 3A substrate simvastatin from the distal parts of the intestine, delayed release film coated tableted oral dosage forms were developed. Simvastatin delayed release tablet, simvastatin immediate release capsule and simvastatin immediate release tablet Zocor were administered as single doses (20 mg) to fasting healthy volunteers in a crossover design.
Results: Simvastatin bioavailability was increased by a factor of three, as compared to the reference formulation Zocor. The overall metabolite levels from the immediate release capsules tended to be higher throughout the period studied than the metabolite levels following administration of Zocor and simvastatin delayed release dosage form.
Conclusions: The interplay between gastrointestinal physiology (lower CYP 3A expression in the distal ileum and the colon) and formulation design (zero-order controlled release after a predetermined lag-time) resulted in successful absorption and bioavailability improvement and represent a viable strategy to reduce the dose of CYP 3A drugs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11095-007-9519-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Programmable Porous Silicon Microparticles for Temporally Staged Drug Delivery in Combination Cancer Immunotherapy.
ACS Appl Mater Interfaces
January 2025
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Combination therapies using checkpoint inhibitors with immunostimulatory agonists have attracted great attention due to their synergistic therapeutic effects for cancer treatment. However, such combination immunotherapies require specific timing of doses to show sufficient antitumor efficacy. Sequential treatment usually requires multiple administrations of the individual drugs at specific time points, thus increasing the complexity of the drug regimen and compromising patient compliance.
View Article and Find Full Text PDFInforming ICU Digital Twins: Dynamic Assessment of Cardiorespiratory Failure Trajectories in Patients with Sepsis.
Shock
January 2025
Department of Industrial and Systems Engineering, University of Florida, P.O. Box 116595, Gainesville, FL, 32611, USA.
Understanding clinical trajectories of sepsis patients is crucial for prognostication, resource planning, and to inform digital twin models of critical illness. This study aims to identify common clinical trajectories based on dynamic assessment of cardiorespiratory support using a validated electronic health record data that covers retrospective cohort of 19,177 patients with sepsis admitted to ICUs of Mayo Clinic Hospitals over eight-year period. Patient trajectories were modeled from ICU admission up to 14 days using an unsupervised machine learning two-stage clustering method based on cardiorespiratory support in ICU and hospital discharge status.
View Article and Find Full Text PDFValence State Hydrogen Channel Enhances Sustained and Controllable Electrocatalytic Hydrogen Evolution in Diabetic Skin Wound Healing.
Angew Chem Int Ed Engl
January 2025
Shanghai Jiaotong University, 800 Dongchuan Road, Minhang District, Shanghai, CHINA.
Diabetes significantly increases the risk of serious health issues, including prolonged skin inflammation and delayed wound healing, owing to inferior glucose control and suppression of the immune system. Although traditional hydrogen (H2) therapy is slightly effective, its ability to tailor the release of H2 on the skin is limited. Accordingly, this study proposed a novel strategy for electrocatalytic H2 release under neutral conditions to promote wound healing in diabetic mice and rabbit.
View Article and Find Full Text PDFComplete traumatic urethral cut and vesicovaginal fistula in a 3-year-old girl, managed by Mitrofanoff procedure: a case report.
J Surg Case Rep
January 2025
Department of Urology, Al-Makassed Charitable Society Hospital, Jerusalem, Mountain of Olives, 97103, Palestine.
We report a 3-year-old patient with urethral cut injury and iatrogenic vesicovaginal fistula following a pelvic fracture; managed with Mitrofanoff procedure. Our patient presented with straining on urination with continuous colorless discharge on her diaper for the past 4 months. Investigations identified vesicovaginal fistulization making a definitive diagnosis of complete urethral injury.
View Article and Find Full Text PDFTwo Imported Malaria Cases with Delayed Response to Treatment in Hatay.
Turkiye Parazitol Derg
January 2025
Hatay Mustafa Kemal University Faculty of Medicine, Department of Parasitology, Hatay, Türkiye.
The study presents two imported malaria cases with a history of travel to malaria-endemic areas and replied late response to treatment. In the blood preparations of the first case, dot-shaped nucleus structures were identified in the erythrocytes, which looked different from the classical erythrocytic forms. In the SD-Pf/Pan test, bands were obtained for both P.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!