Materials for Pharmaceutical Dosage Forms: Molecular Pharmaceutics and Controlled Release Drug Delivery Aspects

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development

Évaluation biopharmaceutique et pharmacocinétique, et modulation du passage transméningé de principes actifs après administration épidurale chez la brebis

La thèse porte sur l'administration d'anesthésiques locaux (ropivacaïne et bupivacaïne) et d'un antidépresseur de plus en plus utilisé pour son effet analgésique (amitriptyline). Les objectifs de la thèse étaient l'évaluation pharmacocinétique et biopharmaceutique de ces principes actifs après administration intraveineuse, intrathécale et épidurale, ainsi que l'amélioration de leur passage transméningé. Différents moyens ont été étudiés afin d'améliorer le passage transméningé, mettant en jeu une modulation pharmacologique par co-administration épidurale avec un agent vasoconstricteur (adrénaline) ou un agent promoteur d'absorption (caprate de sodium). Une modulation pharmacocinétique a consisté à fabriquer et évaluer des microsphères d'anesthésique local après administration épidurale. La biodisponibilité intrathécale après administration épidurale est faible (11.1% pour la ropivacaïne et 1.8 pour l'amitrityline). L'utilisation d'un vasoconstricteur augmente les concentrations intrathécales des anesthésiques locaux. L'influence du promoteur d'absorption sur les concentrations intrathécales est faible. Par rapport à d'autres techniques d'administration épidurale une augmentation de l'AUC intrathécale a été observée après l'administration des microsphères de ripovacaïne. La co-administration épidurale de vasoconstricteur et l'administration sous forme microparticulaire semblent être les techniques les plus intéressantes en clinique.The aim of this thesis consisted in a biopharmaceutical and pharmacokinetic evaluation of local anesthetic drugs, i.e. ropivacaine and bupivacaine, as well as antidepressant drug amitriptyline following intraveinous, epidural and intrathecal administration. This work also consisted in trying to enhance their transmeningeal uptake. Diferent ways of enhancement have been studied, such as drug pharmacological modulation by co-administration with a vasoconstrictor (epinephrine) or with an absorption enhancer (sodium caprate). A modulation of drug dosage form was also performed using local anesthetic-loaded microspheres after epidural administration. Intrathecal bioavailability after epidural administration is low (11.1% and 1.8% for ropivacaine and amitriptyline, respectively). After co-administration with the vasoconstrictor, intrathecal concentrations of local anesthetics were higher. The influence of the absorption enhancer on tne intrathecal concentrations of ropivacaine was low. Compared to other epidural administration practices, such as sequential boluses or bolus followed by infusion, intrathecal ropivacaine AUC was the highest when the drug was administrated in microspheres. Vasoconstrictor epidural co-administration and drug delivery as controlled release systems seem interesting for clinical practice.RENNES1-BU Santé (352382103) / SudocSudocFranceF

Increased risk of renal stones in patients treated with atazanavir.

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Relapses of Immune Thrombocytopenia after the Second and Booster Doses of BNT162b2 Vaccine

We present here a 65-year-old male patient known for immune thrombocytopenic purpura (ITP) and fluctuating platelet count who experienced a severe exacerbation of thrombocytopenia following BNT162b2 COVID-19 vaccination. One month after the second dose, he presented petechiae and asthenia with isolated thrombocytopenia (platelet count: 3 × 109/L). He recovered after a 4-day course of intravenous corticosteroid treatment and intravenous immunoglobulin therapy. Eight months later, his platelet count was within the normal range, and he received a booster dose of vaccine after premedication with prednisone. Eight days later, his platelet count dropped to 29 × 109/L, but he remained asymptomatic. He received a rescue treatment with prednisone followed by rituximab over 4 weeks, allowing progressive improvement. Our case suggests a strong association between COVID-19 vaccination and the exacerbation of ITP

Electrocardiographic and hemodynamic effects of intravenous infusion of bupivacaine, ropivacaine, levobupivacaine, and lidocaine in anesthetized ewes.

International audienceBACKGROUND AND OBJECTIVES: Neural blockade techniques are associated with a risk of acute cardiac toxicity after accidental intravenous (IV) injection of local anesthetics. The aim of this study was to compare electrocardiographic (ECG) and hemodynamic (HEM) effects induced by IV infusion of local anesthetics in an anesthetized ewe model. METHODS: Thirty-two anesthetized ewes received IV bupivacaine (BUPI), ropivacaine (ROPI), or levobupivacaine (S-BUPI) at an equimolar dose, or lidocaine (LIDO) at a 3-fold higher rate (n = 8 in each group). RR, PR, QRS, and QT intervals (QTc), changes (Delta) in systolic and diastolic arterial pressure (SAP and DAP), and in myocardial contractility (dP/dt), were assessed every 30 seconds for 7 minutes. From main ECG variables (RR, PR, QRS, QT), we proposed to use multiple correspondence analysis and hierarchical ascending classification to explore the structure of statistical dependencies among those measurements, and to determine the different patterns of ECG and HEM changes induced by infusion of BUPI, ROPI, S-BUPI, and LIDO. RESULTS: Graphic representation of multiple correspondence analysis associated BUPI with the most pronounced modifications in ECG and HEM variables, followed by in decreasing order ROPI, S-BUPI, and LIDO. Comparisons of clusters identified by hierarchical ascending classification confirmed this classification for ECG variables. Ventricular tachycardia occurred only in the BUPI group. CONCLUSIONS: In our anesthetized ewe model, high dose IV infusion of BUPI induced the most marked changes in RR, PR, QRS, QT, QTc intervals, DeltaSAP, and DeltadP/dt. ROPI altered ECG variables less than BUPI but more than S-BUPI. LIDO was associated with the smallest changes

Population Pharmacokinetics of Amitriptyline After Intrathecal, Epidural, and Intravenous Administration in Sheep:

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