GVK BIO High Throughput Capabilities of In vitro ADME Services

Information about GVK BIO High Throughput Capabilities of In vitro ADME Services

Published on July 22, 2014

Author: gvk_bio

Source: authorstream.com

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PowerPoint Presentation: A D M E S e r v i c es GV K B I O I n v i t r o ADME s c r e e n ing s e r v ice o ff e r s a por t f o l i o o f a u t om at ed Hi g h t h rou ghp ut a ss a y s f o r i n v e s t i g a t i n g : m e t a b o l i s m , d i s t r i b u ti on a n d t o x i c i t y, p e rm e a b i l i t y , s o l ub i l i t y & p h y s i c o c h e m i c a l prop e r t i e s . We d e l i v e r c o n s i s t e n t , acc ur at e c o m pou n d da t a w it h c o s t - e ff i c i e n c y. In v i t r o A DME C a p a b i l i t i es P h y s i c o c h e m i c a l s t u d i e s L o g D / L o g P S o l u b i l i t y ( K i n e t i c / E q u i l i br i um ) C h e m i c a l s ta b i l i t y B i o l og i c a l m a t r i x s ta b i l i t y ( s e r u m / p l a s m a / m i c r o so me s / b l ood / h e p at o c y tes / tis su e h o m o g e n at es ) A b s orp t i o n / D i s t r i b u t i o n A ss a y s C ac o 2 a n d PAMP A p e r m e a b i l i t y T is s u e p e r m e a b i l i t y s t u d ie s- Fr a n z D if f u sion a s s a y P g p s ub st r a te / i nh i b i t or a s s a y s Pr o te i n b i n d i n g B l ood / P l a s m a P a r t i ti o n ing R a t i o M e t a bo l i s m / E x c r e t i o n s o f t w a r e L o g D / L o g P L o g D is d e t e r m i n e d b y the s h a k e -f l a s k m e t h o d , b y d i ss o l v i n g so m e o f t he s o l u t e in a v o l um e o f o c t a n o l a n d w at e r / b uf f e r a n d mea sur e t h e conc e n t r ati o n o f the s o l u t e in eac h s o l v e n t . L o g D is d et e r mi ned b y HP L C - U V w i t h c o n f i r m a tion b y m a ss . So l u b i l i t y S o l ub i l i t y is o n e o f t h e m os t i m p or t a n t p h y s i c o c h e m i c a l prop e r t i e s . We de term i n e e q u i l i b r i u m s o l ub i l i t y b y d r i e d DM S O m e t h od . We can a l s o d ete r mi n e s o l ub i l i t y in a q u e ou s b u f f er ( p H 1 - 9 ), o r g a n ic s o l v e n t s ( D MS O , E t h a n o l, e t c ) , f o rm u l a t i o n s a n d e x c i p i e n t s b y pI O N / M u l t i s c r ee n / H P LC - U V / MS / MS - MS m e t h od s . P r o te i n B i nd i n g In v itr o b i n d ing st ud ie s w i t h p l a s m a h a v e p r o v en to b e a v a l u a b l e t o o l f o r pr e d i ct i ng I n v i v o pr o tei n b i n d i n g . We d e t erm i n e t h e pr o tei n b i n d i n g b y b o t h u l t r a f i l t r a t i o n a n d ra p id e q ui l i br i u m d i a l y s i s . Us ing R ED d e v i c e w e d ete r m i n e pr o tei n b i n d i n g in T h e P a r a ll e l A r t i f i c i a l Me m b ra ne ( P AM PA) is u s ed as a n in v i t r o P e rm e a b i l i t y A ss a y m od e l o f p a s s i v e , t r a n s c e ll u l a r p e rm e a b i l i t y a n d a l s o f o r t he p r e d i c t i o n of Half life / c le a r a n c e d e t e r mi n a t i on u sing Mi c r o s o m e s / H e p a t oc yt e s / S9 fr ac t i o ns / C Y P ac r o ss s p ec i e s ( H u m a n / m ic r o s o mes , p l asm a a n d t i ss u e ho m og e na t e ac ro s s var i o u s R a t / M ou s e / Dog / m on k e y) s p ecies ( R a t / M o u s e / H u m a n & C Y P I nh ib i t ion ( C Y P 1A 2 , C Y P2C 9, C Y P 2C1 9 , C Y P2 D 6 , D o g ) . C Y P 3 A 4 a n d 2 C8) P a t h w a y de te r m i na t i o n ( P h as e I a n d P h a se II ) M e t abol i t e i d e n t i f ica ti on wi t h Microso m e s / H e p a t oc yt e s a n d S9 fr ac ti on ac r o ss s p ec i es ( H u m a n / R at / M ou s e / D o g / M o n k e y ) u sing L ig h t S i gh t M e t I d P A M P A ( P ara l l e l a r t i f i c i a l mem b r a n e p ermea bili t y a s sa y) or a l ab s o rpti on p e rm e a b i l i t y ( lo g M u l t i s c r e e n / a n d b r ain Pe) m a y b e p e n e t r a t i o n . m ea s u re d E ff e c t i v e b y p I O N / LC M S . PowerPoint Presentation: A D M E S e r v i c es M ic r o so m a l S t a b i l i t y M e t a b o l i c s t a b i l i t y p l a y s a n impor t an t r o l e i n t h e s u c ce s s o f d r u g c a n d i d a t e s . F i r s t p a s s m e t a b o l i s m i s o n e o f t h e m a j o r ca u s e s o f poo r or a l b i o a v a i l a b i l i t y a n d s ho r t h a l f l i f e a n d t h e s t u d y i n f l u e n c e s b o t h or a l b i o a v a i l a b i l i t y a n d h a l f l i f e. T h e h a l f l i f e / c l e a r a n c e/ p e r c e n t a g e m e t a bo l i z e d can b e de t ermined i n m i c r o s o m es / S 9 fr a c t i o n s / h e p a t o c y t es . H e p a t oc y t e m e t a b o l i c s t a b i l i t y Per or a l l y a dmi n is te r ed d r u g m a y u n d e r g o f i r s t - p a s s m e t a b o l i s m w h i c h i n f l u e n c e s t h e p h a r m a c o k i n e t i c p r op e r tie s s u ch a s t h e c l e a r a n c e , t h e h a l f - l i f e o r t h e b i o a v a i l a b i l i t y. C r y op re s er v ed hepa t o c y te s are u s ed t o c a l c u l at e h a l f l i f e/ c l e a r a n c e / p e r c e n t a g e pa r e n t c o m po u n d r e m a i n i n g . C YP I nh i b i t i o n C YP i nh i b i t i o n o cc u rs e i t h e r as r e v e r s i b l e i n h i b i t i o n , q u a s i i rr e v e r s i b l e i nh i b i t i o n o r i rr e v e r s i b l e i nh i b i t i o n . C Y P i n h i b i t i o n is a f l u or es c e n t /L C MS b a s ed a ss a y. S p e c i f i c is o f o r m s o f C YP ( C Y P 1 A 2 , CY P2 C 9, C Y P 2 C 1 9 , C Y P 2 D 6 , C Y P 2 C8 a n d CY P3 A 4 ) a r e u s ed t o de te rm i n e t h e i nh i b i t i o n (I C 5 0 ). M e t a b o lit e i d e n ti fica ti o n u s i n g L i g h t S i g ht So f t w a r e I n v i t r o m e t a bo l i t e i d e nt i f i c a t i on & c h a r a c t er i za t i o n o f t h e t e s t c o m pound s are d et er m i n ed u s i n g Q tr a p wi t h L i g h t S i g h t M e t I d s o f t w a r e . H T S B i o a n a l y s i s T h e m et h o d d e v e l op m e n t f o r H T S A D M E i s p e r f or m e d u s i n g D is c o v e r y Qu a nt So f t w a r e . L C - M S /MS 3 2 0 0 Q T R A P A P I 30 0 0 A P I 40 0 0 H P LC A g i l e n t 1 2 0 0 RR LC w it h P D A S h i m a d z u Pr o m i n e n c e w i th UV A g i l e n t 1 2 0 0 RR LC w it h HTS P A L O t h e r s S p e c t r a m a x ( M o l e c u l a r D e v i ces) BM G P o l a r s ta r To m tec Q u a d r a 4 L i qu id H a n d l e r A bo u t G V K B I O GV K B i o s c i e n c es , I n d i a ’ s p re m ier C o n t r ac t R e s e arch O r g a n i z at i o n , d e l i v e r s i n t e g r a t e d r e s ea r c h s e r v i c es . T h e c o m p a n y a cc e l e r a t e s t h e D r u g Dis c o v e r y a n d D e v e l op m e n t p r o c e s s o f i t s c us t o m e r s th roug h s cie n ce a n d i n n o v a t i o n . S er v i c e s C h e m i s t r y S e r v i c e s Pr o c e s s R &D a n d C us tom S y n t h e s i s B i o l o g y I n f or m a t i c s C li n i c a l R e s e a r c h C li n i c a l P h a r m a c o l o g y Co n t a c t : bdb i o @ g v k b i o . c o m V i s i t : www . g v k b i o . c o m

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