Safety, Tolerability, and Pharmacokinetics of Single Doses of Exidavnemab (BAN0805), an Anti-α-Synuclein Antibody, in Healthy Western, Caucasian, Japanese, and Han Chinese Adults.

Exidavnemab is a monoclonal antibody (mAb) with a high affinity and selectivity for pathological aggregated forms of α-synuclein and a low affinity for physiological monomers, which is in clinical development as a disease-modifying treatment for patients with synucleinopathies such as Parkinson's disease. Safety, tolerability, pharmacokinetics, immunogenicity, and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including single intravenous (IV) (100 to 6000 mg) or subcutaneous (SC) (300 mg) administration of exidavnemab in healthy volunteers (HVs). Across the two studies, a total of 98 Western, Caucasian, Japanese, and Han Chinese HVs were enrolled, of which 95 completed the study.

A pharmacometrics approach to assess the feasibility of capillary microsampling to replace venous sampling in clinical studies: Tafenoquine case study.

Aim: Microsampling has the advantage of smaller blood sampling volume and suitability in vulnerable populations compared to venous sampling in clinical pharmacokinetics studies. Current regulatory guidance requires correlative studies to enable microsampling as a technique. A post hoc population pharmacokinetic (POPPK) approach was utilized to investigate blood capillary microsampling as an alternative to venous sampling.

Systematic Evaluation of the Effect of Formulation Variables on In Vitro Performance of Mometasone Furoate Suspension-Metered Dose Inhalers.

The therapeutic benefits of metered dose inhalers (MDIs) in pulmonary disorders are mainly driven by aerosol performance, which depends on formulation variables (drug and excipients), device design, and patient interactions. The present study provides a comprehensive investigation to better understand the effect of formulation variables on mometasone furoate (MF) suspension-based MDI product performance. The effects of MF particle size (volume median diameter; X) and excipient concentration (ethanol and oleic acid, cosolvent, and surfactant, respectively) on selected critical quality attributes (delivered dose (DD), fine particle dose of particles lesser than 5 µm (FPD < 5), ex-throat dose and median dissolution time (MDT)) were studied.

Nose-to-Brain Delivery of Diazepam from an Intranasal Aqua-Triggered In-Situ (ATIS) Gelling Microemulsion: Monitoring Brain Uptake by Microdialysis.

Background And Objectives: An innovative intranasal aqua-triggered in-situ (ATIS) gel is a polymer-free in-situ gelling microemulsion which gels instantaneously on contact with minute quantities of water to form a mucoadhesive gel. The objective of the study was to develop ATIS diazepam (ATIS-diazepam) as an alternative to the injection for epileptic emergencies and evaluate its brain uptake and nose-to-brain targeting efficiency in rats.

Methods: ATIS-diazepam (1 mg/100 µL) was prepared and characterized for in vitro formulation characteristics.

Exploring Peyer's Patch Uptake as a Strategy for Targeted Lung Delivery of Polymeric Rifampicin Nanoparticles.

Uptake of nanoparticles through Peyer's Patches following oral administration could enable translocation through lymph to lymphatic organs like the lungs. An important consideration, however, is nanosize and particle hydrophobicity. Furthermore, as delivering the nanoparticles to the intestine where the Peyer's Patches are localized is important, their intact and rapid transit through the stomach into the intestine is highly desirable.

Bioenhanced advanced third generation solid dispersion of tadalafil: Repurposing with improved therapy in pyelonephritis.

Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN.

Rifampicin Lipid-Polymer hybrid nanoparticles (LIPOMER) for enhanced Peyer's patch uptake.

The oral uptake of intact nanocarriers through Peyer's patches is an important uptake pathway. We report Rifampicin Lipid-Polymer hybrid nanoparticles (RIF-LIPOMER) using glyceryl monostearate as lipid and the mucoadhesive polymer, Gantrez, with the objective of balancing hydrophobicity and mucoadhesion for enhanced Peyer's patch uptake. RIF-LIPOMER was optimized for size, hydrophobicity, and mucoadhesion using Box-Behnken.

In situ hybrid nano drug delivery system (IHN-DDS) of antiretroviral drug for simultaneous targeting to multiple viral reservoirs: An in vivo proof of concept.

We report In situ hybrid nano drug delivery system (IHN-DDS) of nevirapine (NVP) for simultaneous targeting to multiple viral reservoirs. The IHN-DDS system was comprised of a preconcentrate containing NVP, lipid, and a surfactant which when diluted with water resulted in the formation of nanoparticles of size range varied from 70 to 1100nm. Transmission electron microscopy and small angle neutron scattering studies of pellet and supernatant obtained after centrifugation of the IHN-DDS revealed spherical shaped nanoparticles and assembled structures, respectively.

Solid Dispersion of Curcumin as Polymeric Films for Bioenhancement and Improved Therapy of Rheumatoid Arthritis.

Purpose: The aim of our study was development of advanced third generation Curcumin self microemulsifying composition solid dispersion (Cur SMEC-SD) with high drug loading, improved stability, rapid in-vitro dissolution and enhanced bioavailability for improved therapy of rheumatoid arthritis.

Method: The Cur SMEC-SD comprising polymers (KollidonVA64[KVA], Eudragits, HPMC and Soluplus) and self microemulsifying composition of surfactant:co-surfactant:oil were coated onto rapidly disintegrating inert tablet core. SDs evaluated for stability, in-vitro release and bioenhancement.

Systematic review of drug utilization studies & the use of the drug classification system in the WHO-SEARO Region.

Background & Objectives: Information available on drug consumption is inadequate in most low and middle income countries. This systematic review was conducted to analyse published work on drug utilization research/studies (DUR) in the SEARO region of WHO for study objectives, methodology, results and recommendations and to identify the need for improving DUR and the use of the ATC/DDD system.

Methods: A literature search for DUR was carried out in biomedical databases (PubMed, Scirus, Scopus and Google Scholar) up to May 2012.

Oleanolic Acid Prevents Increase in Blood Pressure and Nephrotoxicity in Nitric Oxide Dependent Type of Hypertension in Rats.

Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear.

Objective: To explore antihypertensive activity of OA in N(ω)-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA.

ICMR programme on Antibiotic Stewardship, Prevention of Infection & Control (ASPIC).

Antimicrobial resistance and hospital infections have increased alarmingly in India. Antibiotic stewardship and hospital infection control are two broad strategies which have been employed globally to contain the problems of resistance and infections. For this to succeed, it is important to bring on board the various stakeholders in hospitals, especially the clinical pharmacologists.

Nimesulide controversy: a comparison of EU and Indian scenario.

Background: Regulatory decision for withdrawal of a drug from market in European Union (EU) or other developed countries poses a challenge to authorities in developing countries specially when decision varies from different countries, such as for nimesulide.

Objectives: To compare and evaluate, benefit and risk data for regulatory action, of nimesulide in India and EU.

Methods: Data on Nimesulide from EU available from Report on EMA website and Indian data from published literature (SCOPUS data base), WHO Vigibase and International Medicines Statistics (IMS) was compared.

Comparative regulatory performance on introduction & withdrawal of drugs in India and EU/internationally.

Background: With globalization and signing of WTO GATT treaty, the market in India has expanded. This has necessitated important regulatory decisions.

Objective: This study aims to determine the gap in introduction and withdrawal of drugs in India and EU.

Clinical pharmacology training in India: Status and need.

Clinical pharmacologists undertake many tasks, and this makes defining a curriculum challenging. This is especially so under the changing circumstances in developing countries, where clinical pharmacology has an expanding role. The clinical pharmacologist may be responsible for conducting ethical clinical trials, supporting the needs of the generic drug industry, providing access to safe, effective and affordable medicines, guiding their rational use, achieving millennium development goals, and supervising medicines management standards for hospital accreditation.

Effect of Viscum articulatum Burm. (Loranthaceae) in Nω-nitro-L-arginine methyl ester induced hypertension and renal dysfunction.

Ethnopharmacological Relevance: Viscum articulatum Burm. is used traditionally in Chinese medicine for treating hypertension.

Aim Of The Study: The present study was designed to evaluate the antihypertensive activity of the methanolic extract of Viscum articulatum (MVA) against N(ω)-nitro-L-arginine methyl ester (L-NAME) induced hypertension in rats.

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350 g) received dexamethasone (20 μg/kg/day s.