Given that administration vehicles and drug formulations can affect drug bioavailability, their influence on the pharmacokinetic profile of lamotrigine (LTG), a newgeneration anti-epileptic drug, was studied in rats. Three different formulations administered intraperitoneally at a dose of 10 mg⁄kg were used: (1) LTG suspended in a 0.25% methylcelulose solution, (2) LTG dissolved in a 50% propylene glycol solution, and (3) LTG isethionate dissolved in distilled water. Plasma and brain homogenate levels were determined in order to evaluate vehicle-dependent drug absorption. The results demonstrated rapid absorption of LTG when it was administered as an aqueous solution, in contrast to a slower and more erratic absorption after the injection of either the lipophilic solution or the suspension. A plasma peak was achieved 15 min post-dose with the aqueous solution, with a brain peak being achieved 15 min later, while with the other formulations both plasma and brain homogenate peaks were reached 2 h after LTG administration. This study suggests that LTG isethionate dissolved in distilled water is the most suitable formulation for successful LTG pharmacokinetic studies in rats.

As it has been previously shown that lamotrigine (LTG) accumulates in the kidney of male rats, the purpose of the present investigation was to characterize the kidney profiles of LTG and its kidney distribution pattern in male rats, in order to confirm if a preferential distribution exists and to analyse if it does or does not affect the LTG systemic pharmacokinetics. Adult male Wistar rats were intraperitoneally injected with 5, 10 and 20 mg/kg of LTG. The concentration–time profiles of LTG in plasma and whole kidney were determined over 120 h postdose. The distribution of LTG in the rat kidney was investigated in another group of rats by measuring LTG levels in the renal cortex and medulla. The LTG plasma concentration–time profiles revealed a linear relationship with dose. However, a slight increase in the LTG elimination halflife with dose was observed. In contrast, a nonlinear relationship was established between LTG kidney levels and the dose administered. Consequently, nonparallel patterns were observed between LTG plasma and kidney profiles. The LTG kidney distribution pattern revealed an accumulation of LTG in the renal cortex. The present study demonstrated that LTG distributes preferentially to the kidneys of the male rat in a dose-dependent manner and suggests that such distribution may slightly affect the systemic kinetics of the drug.

The aim of this study was to perform a pharmacokinetic/pharmacodynamic (PK/PD) modelling of lamotrigine following its acute administration to rats. Adult male Wistar rats were given 10 mg/kg of lamotrigine intraperitoneally. Plasma and brain samples were obtained at predetermined times over 120 h post-dose and analysed by liquid chromatography. The anticonvulsant profile against maximal electroshock seizure stimulation was determined over 48 h after dosing. As a linear relationship between lamotrigine plasma and brain profiles was observed, only the plasma data set was used to establish the PK/PD relationship. To fit the effect–time course of lamotrigine, the PK/PD simultaneous fitting link model was used: the pharmacokinetic parameters and dosing information were used in the one-compartment first-order model to predict concentrations, which were then used to model the pharmacodynamic data with the sigmoid Emax model, in order to estimate all the parameters simultaneously. The following parameters were obtained: Vd ¼ 2.00 L/kg, kabs ¼ 8.50 h)1, kel ¼ 0.025 h)1, ke0 ¼ 3.75 h)1, Emax ¼ 100.0% (fixed), EC50 ¼ 3.44 mg/L and c ¼ 8.64. From these results, it can be stated that lamotrigine is extensively distributed through the body, its plasma elimination half-life is around 28 h and a lamotrigine plasma concentration of 3.44 mg/L is enough to protect 50% of the animals. When compared with humans, the plasma concentrations achieved with this dose were within the therapeutic concentration range that had been proposed for epileptic patients. With the present PK/PD modelling it was possible to fit simultaneously the time-courses of the plasma levels and the anticonvulsant effect of lamotrigine, providing information not only about the pharmacokinetics of lamotrigine in the rat but also about its anticonvulsant response over time. As this approach can be easily applied to other drugs, it becomes a useful tool for an explanatory comparison between lamotrigine and other antiepileptic drugs.

A polimedicação aumenta o risco de reações adversas, interações e uso incorreto dos medicamentos. Nos idosos é bastante prevalente, potenciando ainda mais os problemas relacionados com os medicamentos, uma vez que estes também resultam das alterações fisiológicas e multimorbilidades do envelhecimento. Sabendo que os anti-inflamatórios não esteroides (AINEs) são fármacos muito usados pelos idosos, foram objetivos deste trabalho caracterizar potenciais interações entre AINEs prescritos e a restante medicação em idosos e criar uma lista de recomendações relacionadas com a monitorização destes doentes, de modo a evitar ou detetar precocemente tais interações. Análise retrospetiva dos dados referentes à medicação prescrita de uma amostra de idosos de uma Unidade de Cuidados de Saúde Primários (Centro de Saúde de Eiras, Coimbra, Portugal) presentes numa consulta médica entre 2 e 16 de janeiro de 2012. Foram revistos os regimes farmacoterapêuticos de 29 doentes a tomar pelo menos 1 AINE, cerca de 3 meses antes da recolha de dados, num total de 37 AINEs prescritos. Foram encontradas 123 interações moderadas e 2 minor. As principais interações ocorreram entre AINEs e diuréticos (17,6%), antagonistas dos recetores da angiotensina (14,4%), bloqueadores da entrada do cálcio (12,0%) e inibidores da enzima de conversão da angiotensina (8,8%). A prevalência de interações entre AINEs foi de 12,8%. Elaborou-se uma lista de recomendações para monitorização dos doentes quando não se podem evitar as ditas interações. Estas interações devem ser tidas em conta no momento da prescrição e cedência de AINEs, pois podem desencadear efeitos negativos tais como alterações renais e aumento da pressão arterial. O farmacêutico pode desenvolver um papel relevante em serviços como a revisão da medicação, para identificar estas interações potenciais, ou no acompanhamento farmacoterapêutico, na gestão destas situações quando devidamente identificadas. Salienta-se a importância da interação positiva com a Medicina Geral e Familiar para a segurança e a eficiência das terapêuticas.

The choice of appropriate animal models for the initial in vivo testing of potential anticonvulsant compounds is one of the most important steps in the successful search for new antiepileptic drugs. The purpose of this paper is to describe the most important aspects to take into account when performing the maximal electroshock seizure (MES) test in the routine laboratory screening of new antiepileptics: the conventional and threshold MES test experimental procedures, the factors affecting experimental data (laboratory conditions, administration vehicles and drug formulations, time after drug administration, and stimulus duration and site of stimulation) and the assessment of anticonvulsant activity are discussed.

A reversed-phase high-performance liquid chromatography assay was developed and validated to determine plasma and brain lamotrigine concentrations allowing pharmacokinetic-pharmacodynamic studies of this new antiepileptic drug in patients and laboratory animals. Lamotrigine and its internal standard were extracted, under alkaline conditions, from plasma and brain homogenate, into ethyl acetate; brain proteins were previously precipitated with trichloroacetic acid. The method was linear between 0.1 and 15.0 mg/l for plasma, with a detection limit of 0.008 mg/l, and between 0.1 and 5.0 mg/l for brain homogenate, with a detection limit of 0.023 mg/l. The method proved to be simple, useful and appropriate, not only for clinical and experimental research, but also for routine monitoring of lamotrigine concentrations in patients.

Polypharmacy – a frequent situation found among the elderly, related to their physiological changes and multiple morbidities – increases the risk of adverse reactions, interactions, drugs misuse and drug-related problems. Knowing that non-steroidal anti-inflammatory drugs (NSAIDs) are widely used among the elderly, the aims of the present study were to assess the potential interactions that may occur between prescribed NSAIDs and other drugs and to create a list of recommendations for monitoring elderly patients taking NSAIDs, in order to prevent or minimize those negative outcomes. With this purpose, a retrospective study was performed at Centro de Saúde de Eiras (Coimbra, Portugal). The study involved the systematic analyses of the medication regimens of a sample of elderly patients selected from the elderly population of this primary health care unit. Eligible subjects were patients aging 65 or more years and at least with one NSAID included in their therapeutic schemes in the last three months. A total of 37 prescribed NSAIDs were found in the 29 patients of the sample. 125 potential NSAID-drug interactions were found: 2 minor and 123 moderate. Most interactions occurred between NSAIDs and anti- hypertensive drugs, such as diuretics (17.6%), angiotensin receptor blockers (14.4%), calcium channel block- ers (12.0%) and angiotensin converting enzyme inhibitors (8.8%). The prevalence of interactions between NSAIDs was 12.8%. These interactions can cause adverse effects with particular manifestations in the elderly, such as renal impairment and increased blood pressure. The pharmacist can develop a relevant role in services such as medication review, to identify these potential interactions, or pharmacotherapy follow-up, in the management of these situations when properly identified. Stresses the importance of positive interaction with General and Family Practice for the safe and efficiency of therapies. 

While new more potent and complex pharmaceutical agents are becoming available, increasing demands on doctors and the health care system, the increase of drug related morbidity and mortality throughout the world and rising costs related with the incorrect use of medicines make it clear that the identification of a practitioner who is available to focus on the management of all of a patient’s medicines would be an important asset to the future of human health. Medicines are precious, but patients need to learn how to use them. It is possible that this will be one of the advantages that the pharmacist, as a medicine specialist, will bring to the health system, i.e. the promotion of the rational use of medicines as laid down in legislation. The correct use of medicines will significantly decrease the negative outcomes of phar- macotherapy, namely untreated health problems, ineffective treatment and unsafe treatment.Pharmaceutical care is a patient-centered philosophy of assistential practice in which the pharmacist, as a health care team member, has responsibilities in patient medication. There are pharmaceutical services that monitor the process of the use of medicines from a preventive standpoint, identifying risk factors and acting within their constraints – dispensing, preventable morbidity indicators, medication review – and there are pharmaceutical services that monitor the outcomes from a reactive standpoint, identifying negative clinical outcomes and acting on their causes – pharmacotherapy follow-up, disease management. The clinical pharmacist will have to develop new competencies in communication, information retrieval, critical analysis, ethical behavior, teamwork and leadership. And, more than ever, the clinical pharmacist will have to be technically competent, which requires solid training in cellular biology, biochemistry, anatomophysiology, physiopathology, pharmacology and pharmacotherapy. The assistential pharmacist will have to learn to systematize and to register its action in each type of service carried out. The main barrier that he will have to overcome will be his own mind. This will not only provide new ways of boosting the professional satisfaction of the clinical pharmacist but will also provide concrete answers to the real situations of patients, who will ultimately receive better care. 

The prevalence of chronic diseases increases with age, and the constant growth of the overall population makes adherence to therapy a major challenge. A solution to the problem of non-adherence to therapy prescribed by the physician population is the implementation, in community pharmacy, of stock monitoring and pharmacist intervention. We evaluated 54 elderly patients treated with at least 3 drugs with an autonomous life. Adherence to drugs prescription was observed by monitoring the patients, counting of medications not administered and historical progress of the lipid profile, blood glucose, blood pressure and cardiovascular risk in the beginning and end of the study. The purpose of this study was achieved in general, since the pharmaceutical intervention contributed to the adherence to therapy, thereby reducing the impact of risk factors associated with cardiovascular disease, and contribute to the promotion of quality of life for the elderly patients.