Joana Bicker

University of Coimbra | UC · Faculty of Pharmacy

During the research and development of new drugs directed at the central nervous system, there is a considerable attrition rate caused by their hampered access to the brain by the blood-brain barrier. Throughout the years, several in vitro models have been developed in an attempt to mimic critical functionalities of the blood-brain barrier and reli...

P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are clinically important efflux transporters that act cooperatively at the blood-brain barrier, limiting the entry of several drugs into the CNS and affecting their pharmacokinetics, therapeutic efficacy and safety. In the present study, the interactions of catechol-O-methyltransfera...

Background Several natural compounds have demonstrated potential for the treatment of central nervous system disorders such as ischemic cerebrovascular disease, glioblastoma, neuropathic pain, neurodegenerative diseases, multiple sclerosis and migraine. This is due to their well-known antioxidant, anti-inflammatory, neuroprotective, anti-tumor, ant...

The importance of drug dosing time in pharmacokinetics, pharmacodynamics, and toxicity is receiving increasing attention from the scientific community. In spite of mounting evidence that circadian oscillations affect drug absorption, distribution, metabolism, and excretion (ADME), there remain many unanswered questions in this field and, occasional...

Central nervous system (CNS) drug development faces significant difficulties that translate into high rates of failure and lack of innovation. The pathophysiology of neurological and psychiatric disorders often results in the breakdown of blood-CNS barriers, disturbing the CNS microenvironment and worsening disease progression. Therefore, restoring...

The pursuit of more potent and efficacious antidepressant therapies is of utmost significance. Herein, the intranasal (IN) route was investigated for sertraline brain delivery, encompassing a comparative pharmacokinetic study after a single-dose administration to mice by IN, intravenous (IV) (4.87 mg/kg) and oral (10 mg/kg) routes, and an efficacy/...

Alzheimer´s disease is a neurodegenerative disease and the most common cause of dementia with no cure or treatment. Therefore, the investigation to find a disease-modifying therapeutic is crucial. From a pathophysiological point of view, AD is characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflamma...

Purpose Amorphous solid dispersions (ASD) for nasal delivery offer the opportunity to increase drug release performance, while using polymers with mucoadhesive properties. The aim of the present study was to apply this solubility enhancement technique to a poorly soluble drug for nasal delivery, while comparing two particle engineering strategies,...

Licochalcone A (Lico-A) is a flavonoid compound derived from the root of the Glycyrrhiza species, a plant commonly used in traditional Chinese medicine. While the Glycyrrhiza species has shown promise in treating various diseases such as cancer, obesity, and skin diseases due to its active compounds, the investigation of Licochalcone A’s effects on...

In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood-brain barrier. Herein, a new nasal-PAMPA model w...

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiop...

Perampanel is a promising antiepileptic drug (AED) for refractory epilepsy treatment due to its innovative mechanism of action. This study aimed to develop a population pharmacokinetic (PopPK) model to be further used in initial dose optimization of perampanel in patients diagnosed with refractory epilepsy. A total of seventy-two plasma concentrati...

Amikacin is the antibiotic of choice for the treatment of Gram-negative infections, namely, those in neutropenic oncology patients. No populational pharmacokinetic studies are currently available reporting amikacin pharmacokinetics in neutropenic oncology patients despite their specific pathophysiological features and treatments. A large-scale retr...

The intranasal route has been receiving greater attention from the scientific community not only for systemic drug delivery but also for the treatment of pulmonary and neurological diseases. Along with it, drug transport and permeability studies across the nasal mucosa have exponentially increased. Nevertheless, the translation of data from in vitr...

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 (n = 115), with resort to a pharmacokinetic drug monitoring approach. The pharmacokinetic parameters of levetiracetam in e...

Alzheimer’s disease (AD) is a well-known neurodegenerative disease characterized by the presence of two main hallmarks – Tau hyperphosphorylation and Aβ deposits. Notwithstanding, in the last few years the views about the drivers of AD have been changing and nowadays age-related vascular alterations and several cardiovascular risk factors have been...

Depression is a common mental disorder. Its treatment with selective serotonin reuptake inhibitors (SSRIs) is effective only in a fraction of patients, and pharmacoresistance is increasing steadily. Intranasal (IN) drug delivery to the brain stands out as a promising strategy to improve current therapeutic approaches by operating as a shuttle to ov...

Scientific evidence that circadian rhythms affect pharmacokinetics and pharmacodynamics has highlighted the importance of drug dosing-time. Circadian oscillations alter drug absorption, distribution, metabolism, and excretion (ADME) as well as intracellular signaling systems, target molecules (e.g., receptors, transporters, and enzymes), and gene t...

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...

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 importan...

The breast cancer resistance protein (BCRP) is an efflux transporter expressed at the apical surface of human brain endothelial cells of the blood-brain barrier (BBB). It was proposed as one of the transporters responsible for the development of drug resistance to several central nervous system (CNS) drugs, including antiepileptic drugs (AEDs). In...

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 carbam...

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 bl...

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease, caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR), which primarily affects the lungs and digestive system. This gene encodes the CFTR protein, a distinctive membrane transporter of the ATP-binding cassette (ABC) superfamily. It functions...

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 leve...

Depression is a life-threatening psychiatric disorder and a multifactorial global public health concern. Current pharmacological treatments present limited efficacy, and are associated with several harmful side effects and development of pharmacoresistance mechanisms. Developing more effective therapeutic options is therefore a priority. This work...

PurposeZonisamide 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...

Direct oral anticoagulants (DOACs) have been commonly used for the treatment of venous thromboembolism and for the prevention of stroke in patients with atrial fibrillation. Despite not being initially recommended, monitoring DOACs plasma concentrations is now recognized as essential in emergency situations and in special populations. Moreover, the...

Immunotherapy with immune checkpoint inhibitors, such as anti-PD-1 drugs, is an area in increasing development for its efficacy and advantages in the treatment of advanced metastatic melanoma. In fact, immunotherapy has been the target of several and recent studies in different types of cancer, namely in melanoma, a globally growing threat. Contrib...

Direct oral anticoagulants (DOACs) are first-line drugs used for the treatment of venous thromboembolism and prevention of stroke in patients with atrial fibrillation. These drugs do not require the regular biochemical monitoring that is mandatory for warfarin, and they exhibit shorter half-lives and have a faster onset of action. Since recent real...

Why is nose-to-brain delivery considered to be a strategy that directly allows the access of antidepressants to the brain? In which circumstances can the intranasal pathway be applicable? Are there any requirements to follow? What triggers the antidepressant market? Which constraints are imposed during discovery programs? What opportunities can ari...

Despite being one of the most commonly prescribed antiepileptic drugs, levetiracetam is marketed in oral and intravenous dosage forms, which are associated to drug-drug interactions and drug-resistant epilepsy (DRE). The purpose of the present study was to assess the potential of the intranasal route to deliver levetiracetam into the brain, due to...

Drug-resistant epilepsy (DRE) affects approximately one third of epileptic patients. Among various theories that try to explain multidrug resistance, the transporter hypothesis is the most extensively studied. Accordingly, the overexpression of efflux transporters in the blood-brain barrier (BBB), mainly from the ATP binding cassette (ABC) superfam...

Background: Breast cancer resistance protein (BCRP, also known as ABCG2) is gaining momentum as a key transporter that restricts the permeability of a large number of therapeutic agents through the blood-brain barrier (BBB). BCRP is highly expressed in the apical membranes of epithelial cells of the small and large intestine, renal proximal tubule...

Aim: To implement pharmacokinetic drug monitoring and individualize the posology of new antiepileptic drugs, the first HPLC-diode array detection method was developed and validated to simultaneously quantify lacosamide, levetiracetam and zonisamide in human plasma. Materials & methods: Preceded by a reproducible liquid-liquid extraction, chromat...

Inhibition of the biosynthesis of noradrenaline is a currently explored strategy for the treatment of hypertension, congestive heart failure and pulmonary arterial hypertension. While some dopamine β-hydroxylase (DBH) inhibitors cross the blood-brain barrier (BBB) and cause central as well as peripheral effects (nepicastat), others have limited acc...

The heterocycles dihydropyrimidin(thi)ones have been under intensive pharmacological research, but their pharmacokinetic properties remain almost unknown. Herein, fifty dihydropyrimidin(thi)ones were submitted to in vitro screening tests using parallel artificial membrane permeability assays (PAMPA) to evaluate their apparent permeability (Papp) th...

The determination of the permeability of drug candidates across the blood-brain barrier (BBB) is a fundamental step during drug discovery programs. The parallel artificial membrane permeability assay (PAMPA) is a high throughput screening tool applied to evaluate the passive permeability and adapted to predict BBB penetration. Herein, a new PAMPA m...

The measurement of catecholamines and their metabolites in biological samples remains a current analytical challenge, in spite of the great diversity of methodologies that have been developed throughout the years. High-performance liquid chromatography is the standard method for their separation and quantification in biological samples, either coup...

For the first time, a selective and sensitive chiral HPLC-UV method was developed and fully validated for the simultaneous quantification of eslicarbazepine acetate (ESL), carbamazepine (CBZ), S-licarbazepine (S-Lic), R-licarbazepine (R-Lic), oxcarbazepine (OXC) and carbamazepine-10,11-epoxide (CBZ-E), in mouse plasma and brain homogenate supernata...

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