Investigation on IRS-19 (sarbach, france) in influenza A virus infection in mice and humans

184 P o t e n t T h e r a p e u t i c a n d P r o p h y l a c t i c E f f i c a c y of F - P A B in M i c e Infected with Human Enteroviruses. M. A g o h I)'2), T. M i z u n o tl, Y. A g o h II, N. S a t o h IJ, T. K u r i m u r a 2> l)Central Research Laboratories, Maruishi Pharmaceutical Co.,Ltd., Osaka, Japan. 2 ) I n s t i t u t e for M i c r o b i a l D i s e a s e , O s a k a U n i v e r s i t y , O s a k a , Japan. T h e s y s t e m i c e f f i c i e n c y of t h e n o v e l a n t i p i c o r n a v i r u s a g e n t F-PAB[l-(4-fluorophenyl)-2-(4-pyridylaminomethyl)benzimidazole] was assessed in a d u l t or s u c k l i n g m i c e i n f e c t e d w i t h h u m a n e n t e r o v i r u s . S i n g l e , d a i l y s u b c u t a n e o u s d o s e s of F - P A B as l o w as i0 m g / k g s i g n i f i c a n t l y ( p < 0 . 0 0 2 5 ) p r e v e n t e d t h e d e v e l o p m e n t of c o x s a c k i e v i r u s B 4 ( 6 3 7 s t r a i n ) - i n d u c e d h y p o g l y c e m i a in a d u l t S J L / J m i c e (7- to 8 - w e e k s old). A n a l y s i s of the v i r u s t i t e r s in t h e p a n c r e a s of a n i m a l s d e m o n s t r a t e d t h a t F - P A B r e d u c e d the t i t e r in a dose-dependent manner when compared with placebo, implying that d i r e c t i n h i b i t i o n of v i r u s r e p l i c a t i o n w a s p a r a l l e l to the l e v e l s of p l a s m a g l u c o s e . In a d u l t B A L B / c m i c e (7- to 8 - w e e k s old) i n f e c t e d w i t h 5 LDs0 of c o x s a c k i e v i r u s B4 (637 s t r a i n ) , i n t r a p e r i t o n e a l t w i c e a d a y d o s a g e r e g i m e n w i t h F - P A B d o s e s as low as 1.25 m g / k g w a s a l s o e f f e c t i v e in s i g n i f i c a n t l y reducing death (p<0.05). W h e n s u c k l i n g C D - I m i c e w e r e i n f e c t e d w i t h 5 LDs0 of coxsackievirus A9 ( B o z e k s t r a i n ) , subcutaneous administration w i t h d o s e as l o w as 0.5 m g / k g (twice daily) significantly prevented paralysis and death (p<0.001). Furthermore, F-PAB was effective even when therapy was initiated 48 to 72 h a f t e r i n f e c t i o n in b o t h a d u l t a n d s u c k l i n g m o u s e m o d e l s . From these findings, F-PAB is expected to have great potential for s u c c e s s f u l t r e a t m e n t of e n t e r o v i r u s i n f e c t i o n in h u m a n s .

185 Investigation on IRS-19 (Sarbach, France) in Influenza A Virus Infection in Mice and Humans O.I. Kubar, L.S. Safonova, S.L. Firsov, L.E. Nikitina, E.A. Brjaneeva, T.I. Ogli and T.V. Bubeneva Pasteur Institute, St. Petersburg, USSR We have shown that IRS-19 (aerosol) has a protective activity against experimental influenza A(H3N 2) infection in mice. Combination of IRS-19 with inactivated bivalent influenza (A, HIN 1 and H3N 2) vaccine increased the level of anti-influenza A antibodies. In double-blind studies in human volunteers with clinical symptoms caused by the live virus vaccine A(H3N2), IRS-19 did not diminish the symptoms but increased the resistance to reinfection and also increased the functional activity of T cells, especially in persons with low level of immunity. IRS-19 treatment for 21 days of patients with chronic sinusitis prevented recurrences of acute sinusitis and other acute respiratory tract infections.

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