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    A d m in is tr a ti o n o f n if ed ip in e w it h '' g ra p ef ru it '' '' ju ic e' ' is tob ea v o id edA D V IC O R 1 (Ko s) (n ia ci nex te n d ed -r el ea se / lo v a st a ti nta b le ts ) N o v emb er2 0 0 3la b el in gW a rn in g sT h e ri sko f m y o p a th y a p p ea rs tob e in cr ea se d b y h ig h le v el s o fH M G -C o A re d u ct a se in h ib it o rya ct iv it y in p la sma . L o v a st a ti n ism et a b o li ze d b y th e C Y P is o fo rm3 A 4 . C er ta ind ru g s, th a t sh a reth is m et a b o li c p a th w a y ca n ra is e th e p la sma le v el s o f lo v a st a ti na n d m a y in cr ea seth e ri sko f m y o p a th y . T h es e in cl u d ecy cl o sp o ri n e, it ra co n a zo le , k et o co n a zo le a n d o th era n ti fu n g a la zo le s, th e m a cr o li d e a n ti b io ti cser y th ro m y ci n a n dcl a ri th ro m y ci n , H IVp ro te a sein h ib it o rs , th e a n ti d ep re ss a n tn ef a zo d o n e, o r la rg e q u a n ti ti eso f '' g ra p ef ru it '' '' ju ic e' ' (g re a te rth a n 1 q u a rt d a il y )P re ca u ti o n sS h o u ldn o t b e a d m in is te re d w it h '' g ra p ef ru it '' '' ju ic e' 'C li n ic a l P h a rma co lo g y :P h a rma co k in et ic s a b so rp ti o nL o v a st a ti n a b so rp ti o n a p p ea rs tob e in cr ea se d b y a t le a st 3 0 %b y'' g ra p ef ru it '' '' ju ic e' '; h o w ev er , th e ef fe ct is d ep en d en t o n th ea m o u n t o f '' g ra p ef ru it '' '' ju ic e' ' co n su m eda n d th e in te rv a lb et w ee n '' g ra p ef ru it '' '' ju ic e' ' a n d lo v a st a ti n in g es ti o nM E V A C O R 1 (Mer ck )(L o v a st a ti n ) ta b le ts Ju n e 2 0 0 2la b el in gC li n ic a l P h a rma co lo g y :A b so rp ti o nL o v a st a ti n is a su b st ra te fo r C Y P 3 A 4 (s ee'' P re ca u ti o n s: D ru gIn te ra ct io n s' ') . '' G ra p ef ru it '' '' ju ic e' ' co n ta in s o n e o r m o reco m p o n en ts th a t in h ib it C Y P 3 A 4 a n d ca n in cr ea seth e p la sma co n ce n tr a ti o n s o f d ru g s m et a b o li ze d b y C Y P 3 A 4 . Ino n e st u d y(1 ), 1 0 su b je ct s co n su m ed2 0 0 m L o f d o u b le -s tr en g th'' g ra p ef ru it '' '' ju ic e' ' (o n e ca n o f fr o ze n co n ce n tr a te d il u te d w it ho n e ra th erth a n th re e ca n s o f w a te r) th re e ti m esd a il y fo r tw od a y s a n d a n a d d it io n a l 2 0 0 m L d o u b le -s tr en g th'' g ra p ef ru it '''' ju ic e' ' to g et h erw it h a n d 3 0 a n d 9 0 m info ll o w in g a si n g le d o seo f 8 0 m g lo v a st a ti n o n th e th ir d d a y . T h is re g im eno f'' g ra p ef ru it '' '' ju ic e' ' re su lt edin m ea n in cr ea se s inth eco n ce n tr a ti o n o f lo v a st a ti n a n d it s b et a -h y d ro x y a ci d m et a b o li te(C o n ti n u ed )T able 4L a b el in g E x a m p le s o f D ru g – G ra p ef ru it Ju ic e In te ra ct io n s (C o n ti n u ed )D ru g n a m eL a b el in g se ct io nL a b el in g(a s m ea su re d b y th e a re a u n d erth e co n ce n tr a ti o n -t im e cu rv e) o f1 5 -f o lda n d fi v ef o ldre sp ec ti v el y (a s m ea su re d u si n g a ch emic a la ss a y — li q u id ch ro m a to g ra p h y / ta n d emm a ss sp ec tr o m et ry ). Ina se co n d st u d y , 1 5 su b je ct s co n su m edo n e 8 o z g la ss o f si n g le -st re n g th'' g ra p ef ru it '' '' ju ic e' ' (o n e ca n o f fr o ze n co n ce n tr a ted il u te d w it h th re e ca n s o f w a te r) w it h b re a k fa st fo r th re eco n se cu ti v e d a y s a n d a si n g le d o seo f 4 0 m g lo v a st a ti n inth eev en in g o f th e th ir d d a y . T h is re g im eno f '' g ra p ef ru it '' '' ju ic e' 're su lt edin a m ea n in cr ea sein th e p la sma co n ce n tr a ti o n (a sm ea su re d b y th e a re a u n d erth e co n ce n tr a ti o n -t im e cu rv e) o fa ct iv e a n d to ta l H M G -C o A re d u ct a se in h ib it o rya ct iv it y [u si n g av a li d a te d en zy m e in h ib it io n a ss a y d if fe re n t fr o m th a t u se d in th efi rs t st u d y , b o thb ef o re(f o r a ct iv e in h ib it o rs ) a n d a ft er(f o r to ta lin h ib it o rs ) b a seh y d ro ly si s] o f 1 .3 4 -f o lda n d 1 .3 6 -f o ld ,re sp ec ti v el y , a n d o f lo v a st a ti n a n d it s (b et a )- h y d ro x y a ci dm et a b o li te (mea su re d u si n g a ch emic a l a ss a y — li q u idch ro m a to g ra p h y / ta n d emm a ss sp ec tr o m et ry ) o f 1 .9 4 -f o lda n d1 .5 7 -f o ld , re sp ec ti v el y . T h e ef fe ct o f a m o u n ts o f '' g ra p ef ru it '''' ju ic e' ' b et w ee n th o seu se d inth es e tw o st u d ie s o n lo v a st a ti np h a rma co k in et ic s h a s n o t b ee n st u d ie dW a rn in g sT h e ri sko f m y o p a th y / rh a b d o m y o ly si sis in cr ea se d b y co n co m it a n t u seo f lo v a st a ti n w it h th e fo ll o w in g :P o te n t in h ib it o rs o f C Y P 3 A 4 : C y cl o sp o ri n e, it ra co n a zo le ,k et o co n a zo le , er y th ro m y ci n , cl a ri th ro m y ci n , H IVp ro te a sein h ib it o rs , n ef a zo d o n e, o r la rg e q u a n ti ti eso f '' g ra p ef ru it '''' ju ic e' ' (g re a te r th a n 1 q u a rt d a il y ), p a rt ic u la rl y w it h h ig h erd o se s o f lo v a st a ti n (s eeb el o w : '' C li n ic a l P h a rma co lo g y :P h a rma co k in et ic s; P re ca u ti o n s: D ru g In te ra ct io n s, C Y P 3 A 4In te ra ct io n s' ')B IL T R IC IDE 1 (B a y er )(p ra zi q u a n te l) ta b le ts A u g u st2 0 0 4 la b el in gC li n ic a l P h a rma co lo g y'' G ra p ef ru it '' '' ju ic e' ' w a s re p o rt edto p ro d u cea 1 .6 -f o ld in cr ea se inth e C m a x a n d a 1 .9 -f o ldin cr ea sein th e A U C o f p ra zi q u a n te lD ru g – d ru g in te ra ct io n sH o w ev er , th e ef fe cto f th is ex p o su rein cr ea seo n th e th er a p eu ti cef fe ct a n d sa fe tyo f p ra zi q u a n te l h a s n o t b ee n sy st ema ti ca ll yev a lu a te dC E N E S T IN 1 (Du ra m ed )(s y n th et ic co n ju g a te des tr o g en s, A ) F eb ru a ry2 0 0 4la b el in gC li n ic a l P h a rma co lo g y : D ru g –d ru g in te ra ct io n sIn h ib it o rs o f C Y P 3 A 4 su cha s er y th ro m y ci n , cl a ri th ro m y ci n ,k et o co n a zo le , it ra co n a zo le , ri to n a v ir a n d '' g ra p ef ru it '' '' ju ic e' 'm a y in cr ea sep la sma co n ce n tr a ti o n s o f es tr o g en s a n d m a y re su ltin si d e ef fe ct scC IAL IS 1 (L il ly IC O S )(t a d a la fi l) N o v emb er2 0 0 3la b el in gP re ca u ti o n s: D ru g – d ru gin te ra ct io n sK et o co n a zo le (4 0 0 m g d a il y ), a se le ct iv e a n d p o te n t in h ib it o r o fC Y P 3 A 4 , in cr ea se d ta d a la fi l 2 0 -mg si n g le -d o seex p o su re(A U C )b y 3 1 2 % . O th erC Y P in h ib it o rs — A lt h o u g h sp ec ifi c in te ra ct io n sh a v e n o t b ee n st u d ie d , o th erC Y P 3 A 4 in h ib it o rs , su cha ser y th ro m y ci n , it ra co n a zo le , a n d '' g ra p ef ru it '' '' ju ic e, '' w o u ldli k el y in cr ea seta d a la fi l ex p o su re .
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    In this paper,we proposed the concepts of me-too drug,me-better drug and me-new drug according to our understanding of drug RD in China.We described the relations among me-too,me-better and me-new drugs,and the relation between innovative degree and economic returns during drug RD as well as the route for drug RD in China.
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    Drug-drug interactions in diabetic patients could be serious, even life threatening. Possible manifestation of hypo/hyperglycemia as a consequence of drug-drug interactions are often wrong interpreted as a nonadherence to the diabetic diet or polymorbidity of the patient. Drug-drug interactions are not taken into account. The risk of drug-drug interactions is exponentially increasing with the number of taken drugs. In the group of diabetic patients is good to prevent the combinations of drugs, which can lead to drug-drug interactions and use alternative therapy with lower potential of drug-drug interactions. In this paper we present the possibilities of clinical pharmacist from the Department of clinical pharmacology to prevent and solve the drug-drug interactions in diabetic patients.
    Pharmacotherapy
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