Tratamento da esquistossomose mansônica hepatesplênica com praziquantel

SUMMARYA random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniqui¬ ne, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitológica! follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were ne gative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated iwith praziquantel and 272 with oxamniquine. The two groups /were homo geneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69. 8% (134/192) with oxamniquine (p > 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamni quine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclu sively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy.

Section: Discussionmentioning

confidence: 99%

“…32 . Actually, the liver function tests re-evaluated six months after the drug administration were improved 10 .…”

Section: Discussionmentioning

confidence: 99%

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

Gl¹

1985

“…COUTINHO & col. 5 , DOMINGUES & COU-TINHO 6 , MOURA &c col. is detectaram distúrbios neuropsiquiátricos (excitação psicomotora, alucinação, alterações do comportamento) e alterações eletroencefalográficas, em indivíduos tratados com oxamniquine. Os Autores justificaram que tais manifestações seriam decorrentes de "estímulos inespecíficos" da droga em indivíduos com patologias neuropsiquiátricas preexistentes.…”

Section: Discussionunclassified

Neurotoxicidade do oxamniquine no tratamento da infecção humana pelo Schistosoma mansoni

Carvalho

Shikanai-Yasuda

Neto

et al. 1985

RESUMOForam tratados com oxamniquine (dose oral única de 12,5 a 15 mg e 15 a 20 mg/kg de peso, para maiores e menores de 15 anos respectivamente) 180 indivíduos com esquistossomose mansoni, matriculados na Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As idades variaram de 5 a 65 anos e as formas clí-nico-evolutivas prevalentes foram a intestinal e hepatointestinal. Os principais efeitos colaterais neuropsiquiátricos foram: sonolência (50,6%), tontura (41,1%), cefaléia (16,1%), amnésia transitória (2,2%), alterações de comportamento (1,7%), tremores (1,1%) e convulsão (1,1%). Em 20 indivíduos foi avaliada a neuroto¬ xicidade da droga através de eletroencefalografia, antes e após o tratamento. Em 3 (15%), foram detectados alterações no traçado, sem contudo apresentarem manifestações clínicas neuropsiquiátricas. Os resultados demonstram ser o oxamniquine determinante de efeitos tóxico-colaterais na esfera neuropsiquiátrica. INTRODUÇÃORICHARDS & FOSTER 7 descreveram em 1969 uma série de derivados aminometiltetrahidroquinoleínicos com ação esquistossomicida.. Desses compostos o que apresentou maior atividade foi o UK-3883 (2-isopropilaminometil-6-metil-7-nitro-l,2,3,4,-tetrahidroquinoleína). Este composto, quando metabolizado organicamente sofre uma hidroxilação no grupamento 6-metil, originando o 6-hidroxometil-2-isopropilaminometil-7-nitro, 1,2,3,4,-tetrahidroquinoleína. Foi denominado inicialmente de UK-4271 e posteriormente, com o nome genérico de oxamniquine.Este composto apresenta elevada ação esquistossomicida e sua obtenção em escala industrial se processa através da hidroxilação do UK-3883, pela atividade biológica do Aspergillus sclerotiorum.KAYE & WOOLHOUSE », estudando o metabolismo do oxamniquine em animais de laboratório e voluntários humanos, concluíram que o medicamento é bem absorvido por via oral e parenteral e que a via de excreção é a urinária, através de dois metabólitos (6-carboxi e 2-áci do carboxílico). A meia vida, medida atravcs de liberação radioativa no sangue após administração oral é de 2 a 6 horas.O oxamniquine foi utilizado inicialmente por via parenteral na dose única de 7,5 mg/kg.(1) Professor-assistente da

“…The potent drugs represented a breakthrought in first one was hycanthone, mainly administered by intramuscular route. Unfortunately, some cases of fatal toxic hepatitis *- 6 and drug re sistance 1^ were reported.…”

Section: Introductionmentioning

confidence: 99%

Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

Silva

Zeitune

Rosa-Eid³

et al. 1986

SUMMARYA double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects -mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea -were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls -three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs -despite their different chemical structures, pharmacological properties and mechanisms-of-action -induce similar sid&effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.