Prediction of drug‐drug interactions using physiologically‐based pharmacokinetic models of CYP450 modulators included in Simcyp software

In recent years, physiologically based PharmacoKinetic (PBPK) modeling has received growing interest as a useful tool for the assessment of drug pharmacokinetics. It has been demonstrated to be informative and helpful to quantify the modification in drug exposure due to specific physio‐pathological conditions, age, genetic polymorphisms, ethnicity and particularly drug–drug interactions (DDIs). In this paper, the prediction success of DDIs involving various cytochrome P450 isoenzyme (CYP) modulators namely ketoconazole (a competitive inhibitor of CYP3A), itraconazole (a competitive inhibitor of CYP3A), clarithromycin (a mechanism‐based inhibitor of CYP3A), quinidine (a competitive inhibitor of CYP2D6), paroxetine (a mechanism‐based inhibitor of CYP2D6), ciprofloxacin (a competitive inhibitor of CYP1A2), fluconazole (a competitive inhibitor of CYP2C9/2C19) and rifampicin (an inducer of CYP3A) were assessed using Simcyp^® software. The aim of this report was to establish confidence in each CYP‐specific modulator file so they can be used in the future for the prediction of DDIs involving new victim compounds. Our evaluation of these PBPK models suggested that they can be successfully used to evaluate DDIs in untested scenarios. The only noticeable exception concerned a quinidine inhibitor model that requires further improvement. Additionally, other important aspects such as model validation criteria were discussed.     

Laser utility in the treatment of hemorrhoidal pathology: a review of literature

Lasers in Medical Science - Hemorrhoidal disease is a common reason for consultation in proctology. It can be treated in several ways (medical, endoscopic, and surgical). Laser treatment has been...     

Enquête de pratique sur l’analgésie péridurale en dehors de l’obstétrique

Objectives

To describe the current use of epidural anesthesia (EA) apart from obstetrics, and to explain the reasons of its low utilization.

Study design

Observational study.

Methods

A survey of practice with a self-questionnaire was sent by e-mail and available on Internet. Answers were compared between groups doing or not an epidural analgesia with exact Fisher tests (P < 0.05 statistically significant).

Results

Among the 176 anesthesiologists who answered to the questionnaire, only 21.4% never used epidural analgesia. The main reasons were alternatives therapeutics such as PCA with opioids or TAP block (24/38 vs. 46/140). TAP block was the most common alternative used by more than 50% of anesthesiologists. Loss of competence (4/30 vs. 0/39) was rarely the reason to its low utilization. The low accessibility to specialized postoperative units was recognized in both groups as a limiting factor to do an epidural but not the fear of neurological complications. Those who never perform epidural analgesia were statistically more often physicians between 40 and 50 years (12/38 vs. 19/140). Heparin, aspirin and clopidogrel are no longer contraindications according to anesthesiologists less than 40 years old (50/68 vs. 31/68; 44/68 vs. 31/68; 37/68 vs. 23/68 respectively) but not for older.

Conclusions

Epidural analgesia is performed more often by younger anesthesiologists. This survey suggests the need of specific postoperative area to allow anesthesiologist to perform and supervise safely this technique. Recommendations of the French society of Anesthesiologists are also poorly applied.     

Clinical Correlates of the Anatomical Relationships of the Foramen Ovale: A Radioanatomical Study

Introduction Endonasal endoscopic transpterygoid approaches are commonly used techniques to access the infratemporal fossa and parapharyngeal space. Important endoscopic endonasal landmarks for the poststyloid parapharyngeal space, hence the internal carotid artery, include the mandibular nerve at the level of foramen ovale and the lateral pterygoid plate. This study aims to define the anatomical relationships of the foramen ovale, establishing its distance to other important anatomical landmarks such as the pterygoid process and columella. Methods Distances between the foramen ovale, foramen rotundum, and fixed anatomical landmarks like the columella and pterygoid process were measured using computed tomography (CT) scans and cadaveric dissections of the pterygopalatine and infratemporal fossae. Results The mean distances from the foramen ovale to columella and from the foramen rotundum to columella were found to be 9.15 cm and 7.09 cm, respectively. Analysis of radiologic measurements detected no statistically significant differences between sides or gender. Conclusions The pterygoid plates and V3 are prominent landmarks of the endonasal endoscopic approach to the infratemporal fossa and poststyloid parapharyngeal space. A better understanding of the endoscopic anatomy of the infratemporal fossa and awareness of the approximate distances and geometry among anatomical landmarks facilitates a safe and complete resection of lesions arising or extending to these regions.