Current Clinical Pharmacology - Volume 9, Issue 4, 2014

Ezogabine (EZG)/retigabine (RTG) and its metabolites are mainly eliminated renally. This Phase 1 study assessed the effect of hemodialysis on the pharmacokinetics of EZG/RTG and its N-acetyl metabolite (NAMR) in patients with end-stage renal disease; tolerability of EZG/RTG was a secondary endpoint. Patients (N=8) received EZG/RTG 100 mg orally 4 hours before (Period 1) or following (Period 2) dialysis. Blood (both periods) and dialysate (Period 1) samples were taken up to 68 hours post dose. Tolerability was assessed throughout both periods. The area under the concentration– time curve (0–68 hours) for EZG/RTG was 33% lower (geometric mean ratio [90% confidence interval]: 0.67 [0.61, 0.73]) on dialysis versus off dialysis and 43% lower for NAMR (0.57 [0.53, 0.62]). Median (range) reductions in plasma concentrations from dialysis start to end were 52% (17–59%) for EZG/RTG and 51% (27–72%) for NAMR. EZG/RTG 100 mg was generally tolerated.

Melatonin is an endogenous neurohormone produced predominantly in the pineal gland. Recent studies have implicated abnormalities in melatonin physiology and the circadian rhythm in individuals with autism spectrum disorders (ASD). These physiological abnormalities include lower nighttime melatonin or melatonin metabolite concentrations in ASD compared to controls. These abnormalities in melatonin concentrations may be directly attributed to variations in melatonin pathway physiology as both functional and genetic variations in this pathway have been reported in children with ASD. Four studies have observed a correlation between abnormal melatonin concentrations and the severity of autistic behaviors. Twenty clinical studies have reported improvements in sleep parameters with exogenous melatonin supplementation in ASD, including longer sleep duration, less nighttime awakenings and quicker sleep onset. A recent meta-analysis of five randomized, double-blind, placebo-controlled crossover trials examining exogenous melatonin supplementation in ASD reported significant improvements with large effect sizes in total sleep duration and sleep onset latency compared to both baseline and placebo. Six studies reported that the nighttime administration of exogenous melatonin was associated with better daytime behaviors. Four studies reported improvements with exogenous melatonin supplementation when other sleep medications had previously failed. Adverse effects of melatonin were minimal to none in the twenty treatment studies. These studies indicate that the administration of exogenous melatonin for abnormal sleep parameters in ASD is evidence-based. Further studies examining optimal effective dosing and timing of dosing are warranted.

Autism Spectrum Disorders (ASD) is a group of life-long neurodevelopmental disorders, with onset before 3 years of age. They are characterized by qualitative impairmentin social interactions, absent or impaired language and communication skills, and present with a wide range of stereotyped, repetitive behaviors. Function and outcome are affected not only by core deficits but by associated behaviors such as hyperactivity, aggression, anxiety, and depression. Increasing evidence indicates that autism is a complex, multifactorial disorder involving the brain and the body, a result of genetic vulnerabilities interacting with environmental factors. Although genetics plays a role, the fact, that the incidence of autism in identical twins is not 100% points to external or environmental factors as contributors. No etiology - based treatment has yet been developed. During the last two decades many educational, psychosocial and pharmacological interventions had been utilized and claimed to be effective and even “curative”. The word treatment should be used with caution, and should stand for interventions that are aimed to help people with ASD to adjust more effectively to their environment. Many studies have indicated that behavioral therapy and medication may be at least partially helpful in the treatment of children with ASD particularly on the symptoms of aggression, hyperactivity and attention. In the light of an approved and well established treatment for ASD, over the past two decades research on the effect of diet and nutrition on autism has been increasing. Particular attention has focused on the role of food additives, refined sugar, food allergies, and fatty acid metabolism. However, the results are conflicting and not conclusive. We present here anupdated review summarizing the potentials and limits of the most frequent nutritional and dietary interventions in the treatment of Autism Spectrum Disorders.

Infants are therapeutic orphans. Many drugs used in infants are used “off-label”, increasing the risk of drug toxicity and suboptimal efficacy in this vulnerable population. This knowledge gap in clinical pharmacology is partly attributed to challenges associated with conducting clinical trials in infants. Consequently, there is a need for novel and efficient study designs more suited to this population. Available literature describing the use of minimal-risk approaches to characterize the pharmacokinetics (PK) of drugs in infants was critically reviewed. Population PK approach with sparse sampling was found to be well established. Other, more recent alternatives, like dried blood spots sampling, opportunistic design, and the use of non-blood matrices are promising strategies with an increasing number of applications in infants. Physiologically based pharmacokinetic modeling provides valuable insight in drug disposition but still needs more prospective validation. Increasing experience with these methods provides understanding of their strengths and limitations and will help improve the design of future PK studies in infants.

The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast® Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product.

The core symptoms of Autistic Spectrum Disorder (ASD) are impairment in reciprocal social interaction, communication, narrow interests, and stereotyped behaviour. These are frequently severe and persistent, although their severity may change over the course of life. Furthermore, the frequently associated symptoms of self-injury, aggressive behaviour, impulsivity, poor attention, anxiety, depression, and sleep disruption, can become a major source of additional distress and interference in functioning. The causes of autism are not yet known, but there is a general consensus that ASDs are highly heritable. Comprehension of the neurobiological basis for autism-spectrum disorders is still in its initial stages: a large body of research, however, has established ASD signs and symptoms are of neurological origin, and suggest that autism is a distributed neural system disorder, which disproportionately impairs many higher order abilities. Currently available medical treatments, primarily address co-morbid symptoms, rather than core symptoms. Thus, in spite of recent advances in psychopharmacology, the treatment approach still has important limits and shows poor efficacy on global outcomes. A potential pathway for improving clinical outcomes is that of the personalised treatment for autism, by using therapeutic drug monitoring (TDM) - a valuable tool for drugs with narrow therapeutic index - as well as systematic genetic background assessment, foreseen in future applications. However, it is already possible to implement an active surveillance programme to address safety concerns and to optimise therapeutic drug interventions in ASD.

Diagnosis of pervasive developmental disorders (PDDs), and above all diagnosis of the different PDD subtypes, is an ongoing challenge in psychopathology. Application of categorical criteria is complex and problematic in the clinical field where the boundaries dividing some of the PDD entities are blurred, creating particular problems for the clinician. A dimensional clinical approach, considering autistic symptom severity, level of functioning, developmental characteristics and symptoms other than the ones typically observed in autism, may be a more suitable approach in the clinical field and could provide the clinician treating these disorders with empirical guidance. To identify the clinical features that might differentiate the PDD subtypes, we conducted a comparative study in a clinical sample of children affected by autism disorder (AD) or pervasive developmental disorders not otherwise specified (PDD-NOS) and a mini critical review of the available literature addressing clinical and psychopathological differences between the two subtypes. The results of both our study and our literature review seem to show little support for the current PDD subtypes. In such a framework, the most significant element in clinical practice appears to be a deep knowledge of the characteristics of the individual in question. By adopting a broad and multi-faceted perspective, it becomes possible to define the most effective rehabilitation treatment. This applies particularly to the pharmacological treatment, since, to date, no specific therapies for PDDs are known and the choice of pharmacotherapy can be decided only on the basis of the patient’s general profile and specific features.

Purpose: In this review, potential benefits of oral ginger for prevention or management of drug- induced nausea and vomiting were evaluated based on the available evidences. Method: By searching medical resources including Scopus, PubMed, Medline, Cochrane central register of controlled trials and Cochrane database systematic reviews, available evidences were collected. Ginger, zingiber, nausea and vomiting were considered as keywords. Results and Conclusion: Various studies have evaluated effects of ginger in prevention and management of nausea and vomiting in different conditions such as pregnancy, chemotherapy, and post-operation. Evidences regarding anti-emetic effect of ginger in prevention and treatment of chemotherapy induced nausea and vomiting are limited and results are conflicting. More randomized clinical trials should be conducted to confirm efficacy of ginger in this regards. Ginger showed promising and attractive effects in preventing post-operative nausea and vomiting at least as add-on therapy. The exact role of ginger as anti-emetic in prevention of post- operative nausea and vomiting can be elucidated by future randomized clinical trials.

Background: Due to the lack of properly tested medicines for children, there is little available information with regards to indications and dosing of medications in children. Aim: To collect data on sources where hospital based pediatricians obtain prescribing information when treating children and the extent of collaboration with the hospital pharmacist. METHOD: Two hundred and fifty pediatricians in different hospitals within different cities in Jordan were asked to fill in a structured questionnaire regarding information sources used when prescribing for children. Results: Questionnaires were collected from 162 (64.8%) hospital based pediatricians, who have completed the questionnaire by the designated date. Most (75.5%) reported that the Lexi Comp's Drug Information Handbook was the source that they most frequently used for drug information when prescribing for in children. The BNF and the BNFc (British National Formulary for children) were found to be the most sources that contain sufficient information that aids pediatricians when prescribing for children. A minority (22%) claimed to consult with the hospital pharmacist when they face difficulties when prescribing for children. Conclusions: Pediatricians rely on different information sources when they prescribe for children. Those sources vary in their reliability in aiding pediatrician when prescribing. Further work should be done in the provision of useful information on pediatric drug therapy to pediatricians. More steps should be taking place to activate collaboration and interaction between pediatricians and pharmacists as well.

Substitution of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with another drug of the same class combined with nucleoside reverse transcriptase inhibitors is a therapeutic strategy that can improve the tolerability of antiretroviral treatment. According to the pharmacokinetic properties of NNRTIs, this substitution generates pharmacokinetic drug interactions between NNRTIs, which could decrease NNRTI exposure and virological efficacy during the introductory phase of the new NNRTI. Pharmacokinetics and clinical data are reviewed to estimate the risk for switching from efavirenz to nevirapine, efavirenz to etravirine, efavirenz to rilpivirine and nevirapine to rilpivirine.