Novel biopharmaceutical development investigations towards drug and formulation performance optimization

For a drug to excerpt pharmacological action after oral intake, it first needs to be released from the formulation, get into solution (dissolve), be absorbed, and reach the systemic circulation. Since only solubilized drugs can be absorbed, and thus have therapeutic effect, the understanding of the dissolution and drug release processes of a drug product is of primary importance. Such understanding allows a robust formulation development with an ideal in vivo performance. In order to meet set standards, the performance assessment of oral drug products, such as dissolution testing, often applies conditions that are not reflective of the in vivo environment. The use of non-physiologically relevant dissolution method during the drug product development phase can be misleading and give poor mechanistic understanding of the in vivo dissolution process. Hence, we hypothesized that applying physiologically relevant conditions to the dissolution test would result in more accurate in vivo predictability for a robust and precise development process. Since the buffering system in the intestinal lumen operates at low molarity values, phosphate buffer at low buffer capacity was used as a first approach to an in vivo relevant parameter. Furthermore, a biphasic system was used, that is, the low buffer capacity medium was paired with an organic layer (n-octanol) to mimic the concurrent drug absorption that happens with the in vivo dissolution. Both poorly and highly soluble drugs in immediate release formulations (ibuprofen and metronidazole, respectively) were tested in this set-up to assess the dissolution in the aqueous medium and the partitioning to the organic phase. Additionally, enteric coated formulations were tested in bicarbonate buffer at the in vivo reported molarities values to assess the impact of buffer species on drug dissolution. The evaluated parameters were the buffer system (bicarbonate buffer vs. phosphate buffer), buffer capacity and medium pH. In all approaches, dissolution was also carried out in compendial buffer for comparison purposes. Our results demonstrate that the USP-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied noncompendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating drug release with improved physiological relevance. Similarly, all the enteric coated formulations displayed a fast release in phosphate buffer and complied with the compendial performance specifications. On the other hand, they all had a much slower drug release in bicarbonate buffer and failed the USP acceptance criteria. Also, the nature of the drug (acid vs base) impacted the dissolution behavior in bicarbonate buffer. This study indicates that compendial dissolution test for enteric coated tablets lacks physiological relevance and it needs to be reevaluated. Thus, an in vivo relevant performance method for EC products is needed. Overall, the findings of this thesis comprehensively demonstrates that meaningful differences in performance and accordance to clinical reports were only obtained when physiological relevant conditions were applied. Hence, our results indicate that the central hypothesis was answered positively

Para que um medicamento exerça a ação farmacológica após a ingestão oral, ele primeiro precisa ser liberado da formulação, dissolver, ser absorvido e atingir a circulação sistêmica. Uma vez que apenas medicamentos solubilizados podem ser absorvidos e, assim, ter efeito terapêutico, a compreensão dos processos de dissolução e liberação de um medicamento é de extrema importância. Tal compreensão permite o desenvolvimento de uma formulação robusta com o desempenho in vivo ideal. Para atender aos padrões regulatórios previamente estabelecidos, a avaliação da performance de formulações orais, como por exemplo, o teste de dissolução, frequentemente aplica condições que não refletem o ambiente fisiológico. O uso de métodos de dissolução não fisiologicamente relevante durante a fase de desenvolvimento do medicamento pode gerar resultados equivocados sem uma compreensão mecanistica do processo de dissolução in vivo. Portanto, a hipótese desse trabalho é que a aplicação de condições fisiologicamente relevantes no teste de dissolução resultaria em uma predição mais precisa da dissolução in vivo para um processo de desenvolvimento robusto e preciso. Uma vez que o sistema tampão no lúmen intestinal possui baixa molaridade, o tampão fosfato com baixa capacidade tamponante foi usado como uma primeira abordagem como um meio de dissolução fisiologicamente relevante. Além disso, foi utilizado um sistema bifásico, ou seja, o meio de baixa capacidade tamponante combinado a uma fase orgânica (n-octanol) para imitar a absorção in vivo. Formulações de liberação imediata contendo fármacos de baixa e de alta solubilidade (ibuprofeno e metronidazol, respectivamente) foram testadas no sistema bifásico para avaliar a dissolução no meio aquoso e a partição para a fase orgânica. Ademais, formulações com revestimento entérico foram testadas em tampão bicarbonato nos valores de molaridades fisiológicos para avaliar o impacto da espécie tamponante na dissolução do fármaco. Os parâmetros avaliados foram o sistema tampão (tampão bicarbonato vs. tampão fosfato), capacidade tamponante e pH médio. Em todas as abordagens, a dissolução também foi realizada em tampão farmacopeico para fins de comparação. Nossos resultados demonstraram que o método de dissolução farmacopeico não foi discriminativo, enquanto o meio com menor capacidade tamponante diferenciou entre as formulações obtidas via granulação úmida ou compressão direta. Ademais, a utilização da fase orgânica no teste de dissolução bifásica auxiliou no controle do pH do meio aquoso. Portanto, os métodos não compendiais aplicados foram mais discriminativos do que as condições de dissolução convencionais. Neste estudo, foi demonstrado como a dissolução bifásica e uma baixa capacidade tamponante podem ser usadas para avaliar as diferenças na performance de formulações. Esta pode ser uma abordagem valiosa durante os estágios iniciais do desenvolvimento de medicamentos para investigar a liberação destes sob condições fisiologicamente relevantes. Da mesma forma, todas as formulações com revestimento entérico exibiram uma liberação rápida em tampão de fosfato e atenderam às especificações farmacopeicas. Entretanto, a liberação do fármaco foi muito mais lenta em tampão de bicarbonato e consequentemente não cumpriram com as especificações farmacopeicas. Além disso, a natureza do fármaco (ácido vs. base) impactou o comportamento de dissolução no tampão de bicarbonato. Este estudo indica que o teste de dissolução convencional para comprimidos de liberação retardada não possui relevância fisiológica e precisa ser reavaliado. Portanto, os resultados desta tese demonstram de forma abrangente que diferenças significativas na performance condizentes com relatórios clínicos foram obtidas apenas quando as condições fisiológicas relevantes foram aplicadas. Esses resultados indicam que a hipótese central foi respondida positivamente

Paresia unilateral do terceiro nervo após uso de Metronidazol oral / Unilateral third nerve palsy after use of oral Metronidazole

Resumo Paciente do sexo feminino, 19 anos, com queixa de diplopia, náusea e vômito de início súbito. Ao exame físico, a paciente apresentava rotação da cabeça para a esquerda e limitação da adução do olho direito, sugerindo paresia do músculo reto medial. Ausência de ptose palpebral ou paresia de outra musculatura ocular extrínseca e sem outras alterações na avaliação oftalmológica. Foi relatado pelo paciente o uso de Metronidazol, duas doses de 500 mg, no mesmo dia em que os sintomas começaram. A ressonância magnética do crânio foi solicitada. O resultado mostrou um cisto da glândula pineal, estando os outros aspectos dentro da normalidade. A paresia do músculo reto medial e diplopia persistiram por 14 dias, mesmo após a suspensão do antibiótico, optando, assim, por iniciar a corticoterapia oral, evoluindo com boa resposta clínica, melhora dos sintomas e regressão da paresia muscular.

Abstract Female patient, 19 years old, with a complaint of diplopia, nausea and vomiting of sudden onset. Upon physical examination, the patient presented herself with the head position rotated to the left and limitation of adduction of the right eye, suggesting paresis of the medial rectus muscle. Absence of palpebral ptosis or paresis of other extrinsic musculature of the eye, and without other alterations in the ophthalmological evaluation. It was reported by the patient the use of Metronidazole, two doses of 500 mg, the same day the symptoms started. The magnetic resonance imaging of the skull was requested. The result showed a cyst of the pineal gland, the other aspects being within normality. The paresis of the medial rectus muscle and diplopia persisted for 14 days, even after the antibiotic was discontinued, thus opting to initiate oral corticosteroid therapy, evolving with good clinical response, improvement of symptoms and regression of muscular paresis.

Neurotoxicidad secundaria a metronidazol: un efecto adverso reversible. Caso clínico / Reversible neurotoxicity secondary to metronidazole report of one case

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

Comparação do efeito do metronidazol tópico 10 por cento associado à nifedipina tópica 0.3 por cento versus nifedipina tópica 0.3 por cento isolada no pós-operatório de hemorroidectomia pela técnica híbrida / Comparison of effect of topical metronidazole 10 percent associated with nifedipine 0.3 percent versus nifedipine 0.3 percent alone in postoperative hemorrhoidectomy by hybrid technique

A hemorroidectomia é uma operação frequente e considerada dolorosa para a maior parte dos pacientes. Metronidazol e nifedipina tópicos têm demonstrado diminuir a dor no pós-operatório, quando aplicados isoladamente. O objetivo deste estudo foi avaliar o efeito do metronidazol e nifedipina tópicos, em conjunto, na redução da dor pós-operatória, na evacuação, no desenvolvimento de plicomas inflamatórios e complicações. Material e métodos: Foi feito um estudo duplo-cego, prospectivo e randomizado, incluindo 42 pacientes. O Grupo 1 utilizou metronidazol 10 por cento associado à nifedipina 0,3 por cento e o Grupo 2 apenas nifedipina 0,3 por cento. A dor foi avaliada utilizando uma escala visual analógica (VAS) nas 12 horas do pós-operatório e nos dias 1, 4, 14 e 28. Resultados: Os pacientes que utilizaram a combinação de medicamentos tópicos tiveram menos dor, menor necessidade de analgesia e dose ingerida de analgésicos, maior precocidade evacuatória, menor desenvolvimento de plicomas inflamatórios e complicações, do que aqueles que usavam nifedipina tópica isoladamente; porém, as diferenças estatísticas não foram significativas. Conclusão: A adição de metronidazol à nifedipina na forma tópica não melhorou os parâmetros avaliados no estudo; no entanto, ambos os tratamentos são justificados para uso no pós-operatório de hemorroidectomia.

Introduction: Hemorrhoidectomy is a frequent operation considered painful for most patients. Topical metronidazole and nifedipine have been demonstrated to decrease postoperative pain when they are applied alone. The aim of this study was to evaluate the effect of topical metronidazole and nifedipine together in reducing postoperative pain, in the evacuation, the development of inflammatory skin tags and complications. Material and methods: A double-blind, prospective, randomized study including 42 patients was performed. The group 1 used 10 percent metronidazole plus 0.3 percent nifedipine and the group 2 used 0.3 percent nifedipine only. Pain was assessed using a visual analog score (VAS) on postoperative hour 12 and at days 1, 4, 14 and 28. Results: Patients who used the combination of topical medications had less pain, less analgesic requirement and a lower dose ingested of analgesics, higher early defecation, lower development of inflammatory skin tags and complications than those who used topical nifedipine alone. Nevertheless, statistic differences were not significant. Conclusion: The addition of metronidazole to nifedipine in topical form did not improve the parameters evaluated in this study. However, both treatments are justified for use in postoperative hemorrhoidectomy.

Metronidazole-induced encephalopathy in a patient with liver cirrhosis / 대한간학회지

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

Giardia lamblia: distribuição de microtúbulos no citoesqueleto de trofozoítos e cistos utilizando taxóide fluorescente / Giardia lamblia: distribution of microtubules on the cytoskeleton of trophozoites and cysts by use of fluorescent taxoid

Giardia lamblia é um protozoário parasito do intestino delgado, agente etiológico da giardiose, o qual apresenta um complexo citoesqueleto composto por microtúbulos. Neste estudo, a distribuição dos microtúbulos no citoesqueleto de trofozoítos e cistos de G. lamblia foi investigada por meio de um taxóide fluorescente, o FLUTAX-2 - um derivado do Taxol que se liga aos dímeros polimerizados de alfabeta-tubulina. O efeito do metronidazol sobre o citoesqueleto do organismo também foi avaliado. FLUTAX-2 foi capaz de se ligar aos microtúbulos de trofozoítos e cistos de G. lamblia, tornando possível a visualização de estruturas do citoesqueleto do microrganismo, como flagelos, funis e disco adesivo. Além disso, FLUTAX-2 marcou os trofozoitos cultivados por diferentes períodos, revelando que o intervalo de 48 horas é o melhor tempo de cultivo. A incubação dos parasitos na presença de metronidazol não demonstrou alteração significativa na marcação microtubular por FLUTAX-2. Nosso grupo já apresentou a marcação pelo FLUTAX-2 em outros protozoários, Trichomonas vaginalis, T. gallinae e Tritrichomonas foetus, e este é o primeiro trabalho a revelar o perfil de ligação em G. lamblia. Os resultados contribuem para o conhecimento de aspectos biológicos e morfológicos do parasito e sugerem perspectivas para o diagnóstico laboratorial da giardiose.

G. lamblia is a protozoan parasite of the small intestine and the etiologic agent ofgiardiosis, which presents a complex cytoskeleton composed of microtubules. In this study, the microtubule cytoskeleton was labeled in trophozoites and cysts of G. lamblia, using a fluorescent taxoid (FLUTAX-2), a derivative of Taxol, which binds to áâ-tubulin dimer polymerized. In addition, the effect of metronidazole on the cytoskeleton of the parasite was also evaluated. FLUTAX-2 was able to labelthe microtubules of trophozoites and cysts, allowing the observation of cytoskeletal structures, such as flagella, funis, adhesive disk, and median body. Moreover, FLUTAX-2 labeled the trophozoites from several different cultivation times, revealing the 48 hours as the best incubation period. The incubation of parasites in presence of metronidazole did not show significant alteration on the microtubulelabeling by FLUTAX-2. We have shown the FLUTAX-2 labeling in other protozoa,Trichomonas vaginalis, T. gallinae and Tritrichomonas foetus, and this is the first report revealing the binding profile in G. lamblia. Our results contribute to the knowledge of biological and morphological features of this intestinal pathogen. Furthermore, our data showed no modification of microtubule profile labeling in presence of metronidazole. Finally, a new perspective for giardiosis diagnosticis suggested, since trophozoites and cysts of G. lamblia were labeled withFLUTAX-2.

[In Vitro anti-Trichomonas activity of Freula assafoetida and garlic extracts]

Trichomoniasis is a disease caused by Trichomonas vaginalis and is the most common sexually transmitted disease after viral sexually transmitted ones. Trichomoniasis is usually treated with oral metronidazole and both patient and her partner should be treated. Considering the probable teratogenic effect of metronidazole and parasite drug resistance, it is necessary to find an alternative medication for treatment of trichomoniasis. In this study in vitro effect of garlic and Freula assafoetida extracts on Trichomonas vaginalis were evaluated. This In Vitro study was done in Yasuj Faculty of Medicine, Yasuj, Iran. Trichomonas vaginalis was cultured in TYI-S-33 medium. Effect of garlic and Freula assafoetida extracts in specified times and concentrations on Trichomonas vaginalis were assessed. Garlic extract was used in 0.1, 0,05 and 0.025 mg/ml while Freula assafoetida extract was used in 2, 1 and 0.5 mg/ml. The inhibitory effect of extract on Trichomonas was assessed by counting the alive parasites 1, 2 and 24 hours after exposure with extracts. Findings of this study showed that hydroalcoholic extract of Freula assafoetida at concentration of 0.5, 1 and 2 mg/ml killed 90% of the parasites in first hour of exposure and garlic extract at concentration of 0.1 mg/ml killed 95% of parasites after 2 hours. Moreover garlic extract killed 90% of parasites at concentration of 0.05, 0.025 and 0.0125 mg/ml after 24 hours of exposure even at low concentration. This study indicated that garlic and freula assafoetida have significat effect on Trichomonas vaginalis, therefore detecting the effective substances of these potent anti-parasitic herbs is recommended

Uso de antimicrobianos locais em periodontia: uma abordagem crítica / Use of local antimicrobials in periodontics: A critical approach

A presença da placa bacteriana representa o principal fator etiológico envolvido na iniciação e progressão da doença periodontal inflamatória. O tratamento instituído para esta patologia baseia-se essencialmente na eliminação dos patógenos periodontais, através do debridamento mecânico. Entretanto, nem sempre a raspagem e alisamento radicular promovem resultados clínicos satisfatórios, guiando o profissional a buscar meios alternativos para este tratamento. Neste sentido surgiram os antimicrobianos de ação local, sendo atualmente empregados: gel de metronidazol, chip de clorexidina, fibra de tetraciclina, esferas de minociclina e gel de doxiciclina Diversos relatos na literatura sustentam o emprego desses dispositivos e comprovam a sua eficácia clínica.No entanto, aspectos como custo e acessibilidade vêm sendo discutidos a fim de avaliar a real aplicabilidade.O objetivo desta revisão de literatura é fazer uma abordagem crítica a respeito da utilização de antimicrobianos locais no tratamento da doença periodontal enfatizando as suas indicações, vantagens, desvantagens, custo, viabilidade clínica e eficácia terapêutica.

Excessive crying and irritability in infants due to drugs

This study was performed to see the extent and magnitude of drug induced excessive crying in infants and to know the causative drugs, from July 2005 to June 2006. It is a prospective and descriptive study. All children under 1 year of age, who presented with excessive crying of recent onset as the main complaint and were receiving some medicines were included in the study. After getting detailed history [particularly drug history], the problem was explained to the parents, the suspected drug was stopped and the patients were called back for follow up after 48-96 hours. If the crying had not stopped, the diagnosis was reconsidered and patient was excluded from study analysis. If the crying had stopped, it was assumed that the drug was the cause of excessive crying. All the included patients were studied for age, diagnosis, month of the year, geographical origin and the causative drugs. A total of 227 patients were included in the analysis; out of this, 44 [19.38%] were less than imonth of age while 183 patients [80.62%] were above 1 month, 143 patients were suffering from upper respiratory infection and 78 from wheezy chest. Majority of the patients presented during winter months. About 3/4th of the patients were from D. I. Khan district but the remaining 1/4th were from nearby and remote districts like Mianwali and Layyah. Most frequent causative drug was Rondec-D drops [Abbot] in 13o patients. Other drugs were various cough preparations, promethazine [Phenergan], brochodilators, anti-emetics, metronidazole, anti-histamines, various herbal preparations, phenolbarbitone and various anti-diarrhoeals in a decreasing order of frequency. This problem can be reduced by avoiding these medicines in below 1-2 years of age. It is therefore recommended that these above drugs should not be promoted for use in infants and Rondec-D drops and other similar preparations may be withdrawn from the market

Comparison of metronidazole and furazolidone against giardia lamblia in children

This study was conducted on children infected by Giardia lamblia to evaluate the effectiveness and side effects of Metronidazole and Furazolidone drugs in Kashan. One hundred twenty two individuals infected with Giardia lamblia were assigned in 2 groups. They were 5-12 years old. Patients were surveyed four weeks following the therapy with Metronidazole and Furazolidone. Results were compared using chi-square method. Of 122 infected patients, 68.8% were urban residents, 43.4% were females and 56.6% were males. Abdominal pain was the most common clinical symptoms [84.2%]. Four weeks after the therapy, the efficacy of metronidazole and furazolidone were 87 and 81.6%, respectively. Malaise [12.9%] and dark urine [25%] was the most frequents side effects of metronidazole and furazolidone, respectively. With respect to the efficacy of antiparasite drugs in the treatment of giardiasis, further studies in different parts of the country are highly recommended

Invitro antitrichomonas activity of Allium hirtifolium [Persian Shallot] in comparison with metronidazole

Trichomonas vaginalis infection is a sexually transmitted infection causing vaginitis and acute inflammatory disease of the genital mucosa. Although Metronidazole resistance in T. vaginalis is well documented, The only drug approved for the treatment of trichomoniasis in some countries is metronidazole. Genus Allium plants including garlic; shallot and onion have had an important medicinal role for centuries. Some study have proven antibacterial, antifungal, antiviral, antiprotozoal and antihelmintic properties of genus Allium plants. at first PSHE and PSDE [persian shallot hydroalcoholic and dichlromethanic extract] was prepared in ethanol/water [50:50] and dichlromethane respectively at cool temperature [10°C]. genus Allium plants extracts were shown to decrease the oxygen uptake, reduce the growth of the organism, inhibit the synthesis of lipids, proteins and nucleic acids and damage membranes. In this study the Minimal Inhibitory Concentrations [MICs] of PSHE, PSDE and metronidazole respectively were 10, 5 and 2micro g/ml. Persian shallot inhibited growth of T. vaginalis at low concentrations and in short times, therefore this plant have some antitrichomonas components [including allicin, ajoene and other organosulfides] that antimicrobial properties of these was proven

Albendazole versus metronidazole in the treatment of patients with giardiasis in the Islamic Republic of Iran

We examined the therapeutic effects of albendazole compared to metronidazole in 120 patients with giardiasis in Hamdan. Patients were randomized to receive albendazole [400 mg, once daily for 5 days] or metronidazole [250 mg, 3 times a day for 5 days]. Demographic data of the patients, results of stool for Giardia trophozoites before and after treatment, and drug side- effects were recorded. After treatment 6 [10.0%] of the albendazole group had trophozoites compared with 14 [23.3%] of metronidazole group [P < 0.05]. Patients in the albendazole group had fewer side- effects while 43.3% of the metronidazole group experienced a metallic taste and 35.0% experienced loss of appetite. Albendazole is an easy, safe and effective treatment for giardiasis

Two Cases of Metronidazole-induced Encephalopathy / 대한소화기학회지

Metronidazole is a 5-nitroimidazole compound known as an antimicrobial agent widely used for the treatment of protozoal infection, anaerobic infection, Helicobacter pylori infection and hepatic encephalopathy. It may produce a number of neurologic side effects including peripheral neuropathy, seizure, encephalopathy, ataxic gait and dysarthritic speech. There have been ten or more reports of metronidazole-induced encephalopathy in the literatures including a few reports of brain imaging changes by magnetic resonance images (MRI). However, none of the case of metronidazole-induced encephalopathy in patients with hepatic encephalopathy has been reported yet. Recently, we experienced two cases of metronidazole-induced encephalopathy in patients with liver cirrhosis caused by chronic hepatitis B, which were diagnosed by brain MRI and MR spectroscopy. In this report, we present 2 cases of metronidazole-induced encephalopathy with MR imaging and MR spectroscopic changes including follow- up imaging performed after the discontinuation of the metronidazole with a review of the literatures.

Open, prospective trial to evaluate the efficacy and safety of combination of metronidazole and povidone comparison to povidone iodine alone in pre-and postoperative sterilisation and surgical wound healing.

An open prospective trial was undertaken among 50 patients to evaluate the efficacy and safety of metronidazole and povidone iodine in comparison to povidone iodine alone in pre- and postoperative sterilisation and surgical wound healing. It was found that the combination of metronidazole and povidone iodine is superior to povidone iodine alone in respect to efficacy, in the study.

Antibioticoterapia sistêmica na terapia periodontal / The systemic use of antibiotics in periodontal therapy

O tratamento antibiótico na periodontia objetiva erradicar ou controlar patógenos específicos. Os candidatos a esse tipo de terapia säo pacientes com diagnóstico recente de periodontite ativa ou com história de recorrência da doença pós-tratamento mecânico/cirúrgico. O risco de indicaçäo do tratamento quimioterápico, baseado somente em aspecto clínicos, achados radiográficos ou análise microbiológica restrita, é a ocorrência de falhas no controle dos patógenes existentes ou no conhecimento de novos microorganismos. A decisäo de usar a antibioticoterapia, bem como sua indicaçäo, estäo expostas no trabalho que segue

Avaliação dos efeitos clínicos e microbiológicos da aplicação tópica de Metronidazol à raspagem e alisamento radicular no tratamento da doença periodontal crônica / Evaluation of clinical and microbiological effects of topical Metronidazole application associated with scaling and root planning in the treatment of chronic periodontal disease

O estudo comparou os efeitos clínicos e microbilógicos da raspagem e alisamento radicular (RAR) com ou sem aplicação de gel de Metronidazol a 25 percento, em pacientes com doença periodontal crônica. Foram inclusos neste estudo cego 11 pacientes com no mínimo 4 sítios em dentes unirradiculares com profundidade de sondagem entre 5-8mm, sangramento à sondagem e BANA positivos. Após RAR, os 70 sítios foram distribuídos aleatoriamente entre os grupos: Grupo 1 - RAR; Grupo 2 - RAR em associação com 2 irrigações com gel de Metronidazol a 25 percento, (Elyzol) 0 e 7 dias. Os parâmetros clínicos de profundidade de sondagem, sangramento à sondagem, índice de placa, índice gengival e nível de inserção relativo foram avaliados antes dos tratamentos, 30, 60 e 90 dias após, e a avaliação microbiológica foi realizada com o Teste BANA antes e 90 dias após os tratamentos. Os resultados demonstraram que ambos os tratamentos promoveram reduções estatisticamente significantes em todos os parâmetros até o final do estudo...