Unveiling the potential of intranasal delivery of renin-angiotensin system drugs: Insights on the pharmacokinetics of irbesartan.

The therapeutic interest of renin-angiotensin system (RAS) drugs for the treatment of neuroinflammation has been recently acknowledged. Nevertheless, most of them display limited passage across the blood-brain barrier (BBB). Therefore, this study investigated the potential of intranasal (IN) delivery of six RAS drugs to circumvent the BBB and attain the brain, envisioning its future use in central nervous system (CNS) neuroinflammatory diseases, such as Alzheimer's disease (AD).

Development and validation of an HPLC-DAD method for the quantification of cannabigerol, cannabidiol, cannabinol and cannabichromene in human plasma and mouse matrices.

Cannabigerol, cannabidiol, cannabinol and cannabichromene are non-psychoactive phytocannabinoids, highly present in , for which numerous therapeutical applications have been described. However, additional pre-clinical and clinical data, including toxicopharmacokinetic and pharmacodynamic studies, remain required to support their use in clinical practice and new therapeutic applications. To support these studies, a new high performance liquid chromatography technique (HPLC) with diode-array detection (DAD) was developed and validated to quantify these cannabinoids in human plasma and mouse matrices.

Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.

Epilepsy is a chronic and debilitating neurological disorder, known for the occurrence of spontaneous and recurrent seizures. Despite the availability of antiseizure drugs, 30% of people with epilepsy experience uncontrolled seizures and drug resistance, evidencing that new therapeutic options are required. The process of epileptogenesis involves the development and expansion of tissue capable of generating spontaneous recurrent seizures, during which numerous events take place, namely blood-brain barrier (BBB) dysfunction, and neuroinflammation.

Clinical Application of Pharmacokinetics to Appraise Adherence to Levetiracetam in Portuguese Epileptic Patients.

Adherence to antiseizure drug treatment determines its effectiveness and safety, and consequently affects patients' quality of life. Herein, we assessed adherence to levetiracetam in Portuguese patients with refractory epilepsy ( = 115), with resort to a pharmacokinetic drug monitoring approach. The pharmacokinetic parameters of levetiracetam in each patient were determined in steady-state while admitted to the hospital.

Pharmacology of lacosamide: From its molecular mechanisms and pharmacokinetics to future therapeutic applications.

Epilepsy is one of the most common brain disorders, affecting more than 50 million people worldwide. Although its treatment is currently symptomatic, the last generation of anti-seizure drugs is characterized by better pharmacokinetic profiles, efficacy, tolerability and safety. Lacosamide is a third-generation anti-seizure drug that stands out due to its good efficacy and safety profile.

HPLC method for the determination of antiepileptic drugs in human saliva and its application in therapeutic drug monitoring.

Epilepsy is one of the most prevalent neurological disorders, affecting approximately 1% of the world population. Despite the availability of dozens of antiepileptic drugs (AEDs) in clinical practice, the number of patients who do not respond to treatment and/or exhibit high pharmacokinetic variability remains significant, highlighting the importance of therapeutic drug monitoring (TDM). Plasma and serum are the main biological matrices applied for the TDM of AEDs, but the necessity of a specialized professional has been an obstacle to sample collection in ambulatory.

Development and application of an HPLC-DAD technique for human plasma concentration monitoring of perampanel and lamotrigine in drug-resistant epileptic patients.

Perampanel is a third-generation antiepileptic drug (AED), while lamotrigine is a second-generation AED. Both drugs are subject to extensive pharmacokinetic variability between different patients. Furthermore, it has been reported that perampanel and lamotrigine may be implied in pharmacokinetic drug-drug interactions with other AEDs such as carbamazepine or valproate, with consequent alterations of plasma concentrations.

Is intranasal administration an opportunity for direct brain delivery of lacosamide?

Lacosamide is well-known as an effective and safe anticonvulsant drug. Nevertheless, there is also evidence of anti-epileptogenic, neuroprotective and antinociceptive properties of lacosamide. It is currently available as oral and intravenous (IV) formulations, and its brain concentrations and therapeutic effects depend on its passage across the blood-brain barrier (BBB).

Pharmacokinetic Monitoring of Levetiracetam in Portuguese Refractory Epileptic Patients: Effect of Gender, Weight and Concomitant Therapy.

Levetiracetam is a second-generation antiepileptic drug, widely used in the treatment of focal and generalized epilepsy due to its pharmacokinetic and safety profiles. Its pharmacokinetic monitoring is ascribed as useful to personalize its dosing regimen. The aim of the present study was to describe, for the first time, the pharmacokinetics of levetiracetam in Portuguese refractory epileptic patients.

Pre-Clinical Assessment of the Nose-to-Brain Delivery of Zonisamide After Intranasal Administration.

Purpose: Zonisamide clinical indications are expanding beyond the classic treatment of epileptic seizures to Parkinson's disease and other neurodegenerative diseases. However, the systemic safety profile of zonisamide may compromise its use as a first-line drug in any clinical condition. Since zonisamide is marketed as oral formulations, the present study aimed at exploring the potential of the intranasal route to centrally administer zonisamide, evaluating the systemic bioavailability of zonisamide and comparing its brain, lung and kidney pharmacokinetics after intranasal, oral and intravenous administrations.