Abstract
Biological response modifiers (BRMs) have particular promise when used in combination with more standard antiviral agents for treatment of viral diseases. Reported here are a series of studies which have used two BRMs in combination with the antiviral drug, ribavirin (l-β-o-ribofuranosyl-1,2,4-triazole-3-carboxamide) in treatment of experimentally-induced phlebovirus (Punta Toro virus) infections in mice. The positive BRMs studied include bropirimine (2-amino-5-bromo-6-phenyl-4[3H]pyrimidinone) given orally at dosages of 25, 50 and 100 mg/kg/day beginning 24 h after virus inoculation. and 7-thia-8-oxoguanosine administered intrapcritoneally at dosages of 6.3, 12.5 and 25 mg/kg/day given 24 and 31 h after virus inoculation. In each experiment. multiple dosages of both BRM and ribavirin were selected to range from ineffective levels to, in certain cases with ribavirin, lethally toxic levels. Ribavirin was always administered orally twice daily for three days starting 24 h after virus inoculation. Both drug combinations were considered synergistic, increasing the therapeutic index compared to either drug used alone, and significantly reducing the evidence of ribavirin toxicity. Efficacy was seen as increased survivors, decreased virus recovery from tissues and blood. and lowered glutamic oxalic and pyruvic transaminase levels in the serum.
Highlights
Modificateurs de Ia reponse biologique en association avec des antiviraux contre des infections virales induites experimentalement
In contrast. the immune modulators used in this study have significant immunostimulatory properties which may be reversing ribavirin's high dosage toxicity by neutralizing the immunosuppression induced by ribavirin
In separate unpublished studies that mice dying from high dose ribavi.rin therapy exhibit significant bleeding into the small and large intestine
Summary
Modificateurs de Ia reponse biologique en association avec des antiviraux contre des infections virales induites experimentalement. Les moclificateurs de Ia reponse biologique (MRB) sont particulierement prometteurs lorsqu'uWises en association avec des agents antiviraux classiques dans le traitement des maladies virales. Sont presentees ici des etudes au cours desquelles deux MRB ont ete utilise en association avec !'antiviral Ribavirine Des posologies multiples des deux MRB et de Ia Ribavirine furent selectionnees. La ribavirine a ete administree par voie orale, deux fois parjour, durant 3 jours, 24 heures apres !'inoculation du virus. Le nombre plus eleve de survivants, Ia quantile moindre de virus prelevee dans les tissus et le sang et des taux abaisses de transaminases glutamiques oxaliques et pyruviques seriques suggerent que le traitement etait efficace
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