RESUMO
A large number of clinical studies have been performed to establish the safety and efficacy of H2-receptor antagonist therapy. Few if any of these studies have attempted to address the rationale for the dosage and/or dosage regimens being studied. This study is the first large-scale clinical trial, the purpose of which is to validate the chosen regimen and to address the issue of an optimal therapy for a specific patient population. A regimen of a single nightly dosage is generally acknowledged to offer the potential for improved patient compliance. Furthermore, recent research had suggested that suppression of nocturnal acid secretion is all that is required to heal duodenal ulcers. Hence such a regimen offered the potential for an effective lowered dosage of cimetidine with minimal interference with gastric physiology, increased safety and substantial efficacy. This multicentre, double-blind, placebo-controlled trial therefore evaluated a 4-week course of single night-time dosage of cimetidine. After 4 weeks of treatment the cumulative, endoscopically proven, ulcer healing rate with an 800 mg regimen was 73%, which was statistically higher and significantly superior to the 41% healing seen with placebo (P less than 0.001). The 400 mg nocte dosage regimen of cimetidine normally used as maintenance therapy was significantly inferior to the 800 mg nocte regimen (P = 0.01), and increasing the dosage to 1600 mg nocte for 4 weeks failed to provide a significant improvement in healing over the 800 mg nocte regimen. This 800 mg nocte regimen provided rapid pain relief, with 75% of the patients being free of night-time pain and 65% free of day-time pain, by the end of the first week. The 400 mg 'maintenance dosage' was unable to provide this degree of rapid, complete and early relief to patients with a duodenal ulcer. Furthermore, increasing the dosage to 1600 mg nocte failed to increase the level of early pain relief significantly, perhaps because the extensive response of duodenal ulcer patients to the 800 mg nocte regimen leaves little room for improvement. Based both on the early symptom relief and the ulcer healing rate during 4 weeks of treatment, it is concluded that an 800 mg night-time dosage of cimetidine may be an optimal regimen for many duodenal ulcer patients, particularly those who in the physician's opinion will benefit from a once-daily regimen.
Assuntos
Cimetidina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Adolescente , Adulto , Idoso , Antiácidos/administração & dosagem , Antiácidos/uso terapêutico , Cimetidina/efeitos adversos , Cimetidina/uso terapêutico , Método Duplo-Cego , Úlcera Duodenal/tratamento farmacológico , Feminino , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Fumar , Úlcera Gástrica/tratamento farmacológicoAssuntos
Resistência Microbiana a Medicamentos , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adulto , Amodiaquina/uso terapêutico , Criança , Cloroquina/uso terapêutico , Humanos , Lactente , Malária/sangue , Panamá , Primaquina/administração & dosagem , Pirimetamina/administração & dosagem , Sulfadimetoxina/administração & dosagem , Sulfonamidas/administração & dosagemAssuntos
Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Amodiaquina/uso terapêutico , Cloroquina/uso terapêutico , Resistência Microbiana a Medicamentos , Humanos , Panamá , Quinina/uso terapêutico , Quinolinas/farmacologia , Fatores de TempoAssuntos
Anopheles , Malária/sangue , Plasmodium falciparum , Plasmodium vivax , Animais , Haplorrinos , Humanos , PanamáAssuntos
Cloroquina/farmacologia , Resistência Microbiana a Medicamentos , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Colômbia , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Malária/epidemiologia , Masculino , Pessoa de Meia-Idade , Medicina Militar , Primaquina/administração & dosagemAssuntos
Malária , Plasmodium vivax/patogenicidade , Animais , Haplorrinos , Insetos Vetores , PanamáRESUMO
Pyrimethamine and primaquine were distributed house-to-house, every two weeks, for a two-year period. The last insecticide spraying of the study area took place 10 months before drug distribution began. No vector control measures were operative during the period of drug distribution. As a result, the malaria prevalence which was 17.4 per cent at the beginning of the trial, dropped to 2.4 per cent in eight weeks and to about 1 per cent in another eight weeks and persisted at the latter level for the remainder of the 49 bi-weekly cycle trial. Clinical malaria disappeared
Although P. vivax malaria disappeared from the study area for 32 weeks in the second year of trial, transmission of P. falciparum malaria was greatly reduced but never completely eliminated
Parasite importation by visitors and new settlers was a constant problem. About 2.1 per cent of all new persons encountered in the area had malaria when first seen
No side effects of suficient severity to prevent taking the drug combination in subsequent cycles occurred, except for complaints of headache and nausea which were ascribed to the drug
Malaria prevalence in the study area decreased about 94 per cent while other areas in the Republic of Panama and the Canal Zone experienced an increased prevalence during the first year of the study(AU)