Long acting somatostatin analogue: Clinical potential for ...downloads.hindawi.com/journals/cjgh/1989/398524.pdf · aum, Shon /mud .1ynJrome, S0macos1a1111 analo,t!tte L'analogue

REVIEW

Long acting somatostatin analogue: Clinical potential for

gastrointestinal disease

ABSTRACT: Nam·e sl,matosrntin ts founJ throughout the gastromtesunal tract and has a wide \'artery oi hiolog1cal actions. Nevcrthell•ss, its short b1ol,)g1cal half- life and limitt·d swbility necessitate tts use, ta continuous parenteral infusion ar:d, thus, ltmm tts chcrarwuttc usefulness The development of long actrng sommost·ttin ,rnalogues have lcaJ to a rc-cxaminatton of the thcrapeutk usefulO('ss of somatosrattn in gastrointcstin,11 discast' Somatostntin analogues appear most hcnefic1al tn prcvcnttng symptoms assrn:tated with neurocndocnnc tumours. In aJditton, case controllt·d studies exist to d emonstrate somatostattn analogue cffcctn·encss m treatment of gastrrnntcstinal hemnrrhagt.•, pancreatic fi~tu la , pancrcatitis, short bowel syndrome and dumping syndrome Can J Gastrocntcrol 1989;3(2):77-81

Key Words: Diarrhea, Dwnp111,1pyndrnme. Fi~tttla. Hemorrhage. ln!t!.11inc, PanLrcaum, Shon /mud .1ynJrome, S0macos1a1111 analo,t!tte

L'analogue a cffet prolonge de la somatostatinc: Potentiel cliniquc pour les maladies gastrointestinales

RESUME: Le somatostatine n,Htm·llt· sc trouve tout le long de 1.1 ,·otc gastrointcstinalc ct ses actions biologiqucs sont multiples ct variccs Neanmoins, sa dcm1-l"IC h1olog1que courte t'l ,a smh1lttt' l11nitee rcqutt•rt qu'on l'uttlise en perfusion parcntalc conti nue, cc qui limite son ucilit<'.· rherapcuttquc La misc au pnmt d'analogucs ;1 effct prolonge a conduit ,1 une rcexamen de l'uttlm• chcrapt•uttquc de la somatostattnL' dam lcs affecttons gnstromtcst111all's. Les analogues de In sommostatinc scmhlcnt parriwlicrcmcnt utilcs dans la prewntion d e~ symptomcs assoc1cs aux tumcur, ncurocndocrincs De plus. Jes crudes de c;is cont rl)lccs 0nt demontrc l'cfficac1tc de, analogues de la somatosuuinc dans le craitemenr Jes hcmorragic~ gastromtcstinales, des fistulcs pancreattques. des p,mcn\ime,. du syndrome dl• l'intcsti n court et du syndrome dt· chassc

Drp,1rrmenr oj Mt'J1s1ne. IJ11•1,1cm of Uc111rur1Hcrnlu,:y. Unn·rrnr~ o/ Alhcrra. EJ111m11C1n , Albatt1

Corrr,f,onJrn,t' anJ rr/mnr, Dr RrdwrJ ,\ fl'dornk. l llllL'r.,HJ of All1r1 !<1 , Drf>,1rlml'tll u/ Mcd1nnr. D11·1\1011 of ( ,asr1·r1r111rrn/o~:v ~Jl) Rohrrr .\lru·wn Re,rarch Rwld111.I(. EJnwnron. Albt:rra ToG 2C2 Tdcphon<' 141.1 l14 l2 o<NJ

Re(e11·ecl /or /iult/1,,111011 Fdm«IT)' 20, Jt)/N A,,c111t:d Fehrn<1n 22. Jl)Hll

N \II\J ..;t1~JAJ()..,l:\ll'-l°'1\t'YCIIC

1erradl'tapepttde tuund thmugh· ,,u1 dw gastromu•,1111,11 tr:t( l ,Hid pnn·

< rt'.1, m 1wrn· l·ndml!, ,111J muco,.11 ncu

r11endt1tr1111· , ell, ( 1-'i ). Somato,tattn is

lt1un,l 1n tlw higlw,t n11Kt't1lrat1011 m gas-

111c tundus .md .1111 rum, pancrt·as ,ind d tll 1dcnu m m dent'iisi ng n 1nl'l'r1tratt0ns

frt,m pn1x1m,1l to distal small 111test1tw

.md rarl'I\' 111 the ,olon (6) S<1matosta1i n-

14 1, rlw pr111t1pal 1<1rm rek•ast'd from

tlw ,tom,Kh S0m.1t<1st,11m rde,hl'd fr(lm ,m;11l 11nt·,11n.il mut'osa ts prl dommanth

st1111a111,tati 11 ·l~. "hneas 11111<mmucnsal

small 1111c,1mal neur.tl structures It is pn•

dnm111,mtly sl1ma111sta11 11- H. As om• of clw rl'gul.11,,ry pepudt·s of the d1gesut·e

trau. It h,1s ,I "1de ,·.mety o f b1ologic.1l act1u11, It h.1, ht'l'll ,hnwn ro rt·dun·

1nrt.·,1111.d mt1til1t~ t 7 ')). enll'ric hormonl'

rt•lc<1sL' (lJ. IL'J. ,plandrnic blo(1dOcm

1111. and 111 h 1h1t sl'c rt·tton by tlw g,1s1m .111tru m J ll) , pancrt·as (lJ) ,rnd tlw small

,llld l.1£1.!l' llltl''i[ll1l'S( 1,,17)

T ht.·,t· propl'rtll's of n;ltlVL' scHnato,l.1·

tin ha\'l' rtsltlted 111 tts hdng cons1dt·red

,ts an .111t1d1arrhl·,il .1gent ,int:L' Jl.)7 \ wht·n Rra:cau and tolleagu,•, I IS) 1su·

l.1ted, 'l'qlll'nccd .111d synthl',tZl'd tlw peptide in,111 hm 11w lwpoth,1lamit t·x·

trac 1. fhe pl'pttdl' ".1, 1111ttallv ll'rnwd gmwth horn1<11w 1ek.1st' mhih1t1nJ,? f,ll ·

tor tCiHRil'l h11t 1s no\\ l'lllllmPnh \,; m ,wn ,ls snma1os1;11111

77

FHlORAI-..

Clinically. nat1\·e ,omacosratin has heL'n most effective as an anudiarrheal 111 hormonally mediated secremry diarrheas. including those produced by rumours secreting vasoact1vc inresnn;il pept1JL' !VIPoma) ( 19). 5-hydroxytryp[()phan (carcino1d syndrome) (20-11). g:1smn (Zollmgt'r-Ellison syndrome) and calct ton1n l mewst:1t1c islet cell carcinoma) 124) In non hormonally mediated diarrhea , howc\'er, it has heen less dfenivt' fmlmg to alter diarrhea mducL'd h\ cholera toxin ( 15)

Although nauve ,om.nosmun ha, hccn sho\\'n m reduce smol Olttput 111 a pancnt with short bowel syndrome. this may han' oc.:urrcd because M)m,1tostat111 ,upprcs,cd the clevatl'd hlood levels ot glu cagon. gastromrcsunal polypeptide and pancreatic polypepmk (16) Unforrun::1tcly, 1he short h1olog1cal half-life ( ! to

3 mm,) and limned srabil1ty of n:lll\'e sommo,wrin nL'Ces,natt' it~ use via connnuous parenteral mfw,ion .ind thus limit its therapeuuc usl'f ulnes,

Recently, an ocmpcptidc long .irnng somatost:uin anal1,guc. SMS 2L"'I t>95. (Sandostatin; Sando: Incl has hL'en synrhcs1:cd fr..,m thL' b1olog1cally act1n' pharmacophone(Figure 11(27) Begin nmg \\'ith the 1solnnon of nat1\·e ,omam statm- Hand the kno\\'IL'dgc 1)1 the mini ma! fragment nt't'ded for h 1ological acuon, scrvernl long actmg somaro,tatln annlogues hnve bt'l'n ,vnd1l',i:ed ( 2~).

although the most l'ffoct1\·e rL'mams SMS 201-995

This annlogue conrn111s [)-phenylalanine at one L'nd nnd an alcohol denva tiw of threo111nc at the other. making it res1stanr to en:ymauc dL'grada11011 ThL' substituuon of P-tryptciphan for L ·tryp tophan in po,1t1on t{ furth~·r reduce, deg radation and L'nhances the long ,Kting

NATIVE SOMATOSTATIN

H2N-i ALA j- GLY - CYS - LYS

effect This agL'nt has heen shown to he more potent and longer acting than native somatoscann and can he adm1111Stered subcutaneously (27-29)

In \'llro, SMS 201-995 has an anusccretory cfkct on intestmal fluiJ and dec· tmlytl' trnm,pnrt similar to that of native ,omatosrann ( 29) SMS 201-995 mhibns elcctrnge111c anion secretion and stimulates neutral sodium and chloride absorption and thus has a porenual for a potent anud1arrheal agent (29). The antidiarrhenl effect of SMS 201-995 1s approximately 60 times more potent than nanve somatosratin and docs nor exhibit the rachyphrlaxsi, seen wnh n.llt\'l' somatostatln.

POTENTIAL GASTROINTESTINAL THERAPEUTIC

APPLICATIONS Cl1n1cal ,tudies with somat<btatin

analogue have. for thL' mo:.t part. beL'n anecdotal. ,rnd doublc-blmJ prospective studies are requ1rL'd hL'fore the full ther· apeunc benefit of this analogue can be dctermmed Although S1'.1S 201-995 does not t.kmonstrate the rnchyphylaxs1s seen \\·1th native somatostat1n, recent rL'porrs have described rdap~e of dwrrhca wccb LO mon ths aftL'r mnial rL's· ponse to S1'.L 201-995 ( 30. 31) This appart'nt dc,ens1ti:auon or down regu-1:Hton m SMS 201-995 remains w be explained Diarrhea due to ncuroendocrine tumours: Somatosrnun analogue. SMS 201-995. has been used successfu lly to control symptons. including diarrhea, of a vast array of neuroL'ndocrinc tumours of thl' gut In ga~tnnomas, c1rculanng gastrin k\'els arc rL'duced, significant sup· prcss1on of aCtd secrcuon caki:s place and diarrhea ts markedly reduced In some

cases, rt'gression o t hepauc metas1asc, haw beL'n idt'ntified ( H-,5)

In \1·atL'ry d1arrhc;i, hypokalc1111a , achlnrhydn;i ,yndrnme. vasoacuve 111testinal pcpude and 11, homologue. peprndmL' hisudme 1sokuc11w, arl' markl·Jly reduced with the l' hangL' in nt't intc,unal secreuon to net absorption and a significant rL'duction 111 "tool weight .ind frequency, with resultant 111dept'ndl·nce from mtravenou, fluid requ1rcml'nts ( H. ,6-41 ). In only one 11f these casL',ol Vlf>omas did a decren,c 111 d1.irrhe:1 continue dL'spice increa,cd va,oacnw 111tt·,t111;il pcpude kvel, 111 the face n( further metastases ( >6)

In the carcinrnd syndrome, ,omatosta· un analogt.:c has ,1gn1hcantly redlKL'd hmh flush ing, unstable angina and diarrhea hy rL'duc111g nrculnung ,l'rotonin and kin1n ll'\els ( > 1.42-44) During mL'ta,tasnc medullnry carcm11ma ot thl' thyr01J, somat1btatm analogue allc\·t,Ht·d the symptoms of nu,hing and diarrhea associated w1th cle\·.ttcd calrnon111 le\' eb hut did not altL'r the course of the disease I 15.44.45)

Somatrn,tatin analogue has also pro· duced nn euglyccmic scatt' in insulmoma and glucagonoma syndromes I>> I In iht glucagonoma syndrome. somatostaun analogue therapy ha, bet'n used to amc liorate the migrawry nccrolyuc dcrmauus () ))

In summary, somatostann anal1it:ue which can bl' adm111is1ered tn an outpanent on an mtcrmment h:i-,1,. ,, prming invaluable 111 patten ts with rare. ncu· rot..'ndocnne ,ecn'ting tumour, b} con· trolling the life thrcatcnmg dinrrh1.:a and vasomotor respOlbt's Furthermore, the p1,tcntial ex1'r.., for ir, u,e 11Hraopcr· an\'clv during ,urg1cal ma111pularion of ncuroendocnne tumour, when large

SMS 201-995

7 ~8

H2N-PHE - els-~ ............. ~ HOOC - CYS - SEA - THR - PHE - m - - ~ ,,....

HO - THA - CYS - ~....--9

10 9 10

Figure I ) S1ruc1urn/ rdarwm/uJ> of >1<111\~ ,om,11mrar111 1-l ,rn.l rl1< ,,nrh.:ri( /ong <1L1111g ,om,110,1<111>1 c111,1lu.~11.:. S.\IS 21.'l l)()~ Tht <'"cnr1,,/ />h<11111<1.-o/1hor( 1s rhe Pl IE, TR/l. LYS THR I(' JraRt11e111 S 11 bli111;11c>11 of D inJ,w1,lw11 Jm L-inJitophan ar />oSlll<Jn H rcJ1;ce., cnunw11c JeRrnJ<J11011

78

amount:, 11! biologtcally acrive pq:nides can he released following su rgical manip

ulation of the tumour The mechanism of acticm pf somatostatin analogue in con

troll111g symptoms of neurocndocrinc

tumours has noc hl'L'n elucidated However. it appc;1rs m he a consequence of

reduced circulating amine and peptide levels.

Dia rrhea w ith n o n e ndocr ine e tio

logy: In pmients with diarrhL'cl not atrrih

urable to neu rnend1,cnnc tumnun,, treat·

mcnt resu lts wnh snmatostatin :in alogue

haw been less dramatic In diarrhea due

co chol.:ra cntcroto;,,.in (46 ). ileosLOmi

147). l!lOamm,nory bowel disca:,c 14KI

and d1ahcnc dia rrhea I unpublished

observations), somatosmtin analogue has

not been effective Nevertheless, the

somacoscatin analogue has been described

co con t rol severe diarrhen as a conse

quence of lll fa n t secretory diarrhea ( 49.

50). cr yprosporic.lia infec t ion in the

acquired immune deficiency syn drome

(55-5 3). nonsccretory ileostomy d iarrhea

( 54.55) diabetic dia rrhea ( 34.56) and in 50";, of cnscs with idiopath ic secrcrory

diarrhea ( 32). Since hormone levels were

not m ·1su recl tn many of these reports,

it is difficult to determine whether the

effect of somatostatin analogue was a con:;eq ucnce of reduced hormonal output or a dm.•ct antidinrrheal action on the

intestine.

In nonnL'Lm 1endocnnc medwted d iar

rhea. the effect 1 ,f somatmtat111 analogue appear, \';inahk and may relate tc, rhL'

inahtl1ty tn achieve thcrapn1t1c drug

levels at the l'nterorytc level

G astroin testinal h e m orrhage: C,111-

trol of bleed111g hy nauve ~orna to~rnt1n

therapy h as hecn reported in hoth nonvaricc:il ,llld \'nnceal hcm1,rrhagcs 111 a

,m::i ll nu mhcr c,f ,tud ic, ( 5 7 ). Scud 1cs w examine the effect of somatoscatin ana

logue on gastromtestinal hemorrhage arL'

even fewer and till' results arc contl1ct·

ing In treatmL'nt of rdapslllg bleedmg pepuc uker, in ,1 patient wi th Zollinger

Ellison syndrome, it was found m he

more potent than n ative somatostmin in

reducing gastnc aCJd secretion and in reducing 1n rcs11nal mucosa! blondflow

for n substan t ially longer period and

resulted in cessation o(bleec.l1ng 1n e ight

o( IL' pauen ts ( 5K, 59 ).

S11mat0starm analogues demonstrated

a lfose dependent effect 1111 till' mortal

try, incidence and intensi ty nf cystearnine

induced duodenal lesions 111 rnrs {60) In conrrast, ,<,matostmin analogue did

1101 dc.'monstratc splanchnic vasocc11btnc

ti vc effects in ,tncsthemcd pigs Llcspite

adc.'quate scrum le\'els {61 J and inhihned naturally occuring vasopressin secre

tion during gastrointesrinal hrnwrrhnge (62).

With the present da), effernvcnL'SS Ill safely ,uppressmg gastric nc1d produc

tion and w1th the adven t of tlwrapcunc endoscopy. it 1s unlikelv that sommosmun

analogues will replnc<' existing therapy for gastrnintcstinal hemorrhage.

P a ncreacic fi stu las: S0matostat111 :ma

logue, haYc hecn demonsrratcd tn p<l·

tcnrly inhihit ex<1crine pancrearic seen'· Lion, b1carbon:nc, protein nnJ Ou1J 111 .1

dnsc dependen t fashion (6 n The treat· me1H of pancrc,1tic cutaneous fistulas

\\ ith somntostatin analogues h;1s been

rcpnned m nine patients (64-69 I In cnch

of th ese cases. fistu la output \\'as cnn,istcncly reduced during somatostat1n an,1·

logul' adm1n1strarinn Nevertheless, Ill

1)nly three of these patten ts \\'as it docu

mL'ntcd that fistulas closL·d as a consc

quenccof Mnnatostmin analogue.1dm1n-1,trarion

Pa n ereatis: In a controlled. douhlc

hlind, multiccntn' trial. nat ive sc1ma111·

,tmin in the treatment cl acute 1>ancrc;u1r1s dcmc,nstrarcd no nd\'antage in

uther the cour,e of the disease or thL' 111orcal1ry (70) Recently, somatostatin

an;.ilogucs h:1ve heen identified to h,\\ L' a cytoprotecti\ e effect on pancrcauc,

bronchial and gastric epithel ium 17 1 ). The mechanism leading to tbsue pro·

tcction h:is nor been clarified. a lthc,ugh

srnhili:ati\,n of cell membrane as well a,

changes 111 amm11 acid sequence mav play

a role

Snmatostalln analogues c1dmin1stcred prior ro varic,us forms of experimental

pancremitis hnve improved survl\·al.

ckmonstrated improved hiswlogical

hl.'a ling ,rnd reduced scrum levels of

lipase and amylase ( 72- 7+ ). Once again,

the mccharnsm of this effect during pan

crcntitis is unkno\\'n hu t may relate to 111hibit1on of pancreatic en:ymc sccrc

uon . Recently. Conwny and colleagues

17 5) demonstrated in dogs th at som:no

statln analogu e produces ;1 prnmpc and

Somatostatin analogue: Therapeutic potential

sustained dccrensc in pancrcauc bloodnow Wi th ou t altCnlllOn 111 systemic hcmodynamics

Sommostaun an.1logucs do nm pres

ently have a role in the 1rea1mc'n1 of acutl' pancreati tis outsidc the clinical research

centre. Neverthcless. their role in preventing pancrea t ius following endo

scopic or surgical manipula11on of the

pancreas remnins to he deter111111cd

S h o r t b owe l syndro m e: A lthoul,!h Dharmsathaphorn ,ind colk:11,!UL''> 17())

demonstrated. as ea r ly as 1982. that narive somawsrntin decreases diarrhea

in patients with short bowel ,yndrome.

only a single case report of a child exist,

to demonstrate the use of long nctlllg ,omatostatin in concrollmg ilenl output

ns a consequence of the short bowel syndrome (77)

Dumping sy ndro m e : S ince M)m;1to

stat1n inh ibits vasonctive pcptidcs and

amines and prevents massive Ouid secre

non into the intestinal lumen. the poten ·

rial therapeu uc effect fo r the treatment oi dumpmg syndrome exists.

The effect of sommostatin analogue Ill I() patients with retractable early clump-

111g and seven patients with severe late

dumpini,: has been examined (78.79). ln

hoth carly and late dumpers, sornatosta· tin anal11guc improved symptoms and

hrearh hydrogen excretion , indicating

,lowing oi gastrointestinal motility. U n

f<)rtunaccly, the J1mimhing rate of gas

inc surgery for peptic ulcer disease may m,1ke a large, double-blmd study to

c'xaminc the effect of ,omarostatin analogue on gnstric dumping difficult to

carry o u t

ACKNOWLEDGEMENT S: Dr l·eJorak 1, a rc'c1r1ent of che Alberta Hernagc foun· Jation fo r Medica l Research cl1111cal mvc,ti· g,llor',htp Th 1, work 1~ supponcd hy i1 grant from the Alberta Hc'nwgc Foundat1lln for Mc'd1C,1l Re,carch The author expresses his ,1ncere appreciarion for che expert st·cretarwl as,1stance of Mr~ Michel Pollard .

REFERENCES I Eide R. Hokklt T, Johansson 0.

Schultzhl'rg M, Efc·nd1c S. Luft R Cellular locali:a11011 tif somatostalln Metabolism 197!U7: 1115-9

2 Dubois MP lmmunoreac11\'c ,ommo· sra1111 is present 111 J1scretl' cells of the cndt,cnne pancreas Pmr Natl Acnd Sci

79

FEDORAK

Ll"A ILJ7'i.72 I , .. !l'). '\ Co,r,1 M. hrrnc·,~.J Snm.11nsrat1 n 1, prt'st'lll 111 ,1 ,uhpopul,111<11\ ul nur· adrc•ncr,.:ic nt·rve fibrl', ,uriplying the 111re,t111c Nc11ro,c1encc llJ84. I'\ lJI 1-9

4 Cosla M. Furnc'"), Lle11'l'llvn-Smith I. Da\"lcs B. Oliwr) An 1mmu1wh1>tll· chemical ,tudy of the pro1,·cuuns of ,om,1tu,taun•co11t:11rnng neuron, m thl' gu1nea·p1g m1,·,mw Nc·un1-,1t'1K,' 1%0.'i:IHI 52

5 !\,lak )M. Pearse AGE. Orinwl,us L. Rloom SR. Arimura A Gw11"1h lwrnl(lnl' rdea,e ·111h1hnmg hornwne in

ga,tro111te,u11;1 l .111d pa11crc·,111c [) cells. Lancer 1975:1 122().4

6 PL'nm,rn E. Wa"J, Buder M. ,·1 al Dis1rihuti<>n ;111d charac1ni~a1ion ol 1mmunorc.1ctive so1nt1to~talin 1n human g;htro1ncest1nal 1r,1ct. Reg Pept ide, ILJ8'\,7:5'\-65

7 Eknd1c S. Matt,llll O E:tfrn ,if ,nma10,rn1i11 011 m1c,11n,1I moril i1y. Ac1n Rad1ol I L1wgn) I "10,kholm) 1971'. 19 HK-'i2

8 J,,hnns,1,n C. Ftcnd1c S. W1,cn 0. U\'an,1,-\\'alle11,1en K, l uf, R f:.flc(is uf ,h,,n-tcrm ,omar,,,raun 111fu,1on on gasrril: and mte,rinal propulsion in human, Scand J Ca,tmt·ntcml 1978.1 > 48 I·>

9 GerichJE. Dam,n GS Som:no,caun phys1nlugy and clinical ,lpplic:111,,n,. Med Clin}J,,rrh Am 1978.h2 ,75-92

10 Bl,,,,m S~ Somaw,umn and rhl' gu1 Ga,rn1e111er,1loin 1978.75 145-7

I I S;1m11wg:ird H, Tv<l,·n C,. Thul111 I , h1m,m L. L'dl'n R Eff.:ct of ,omawst,llin 1111 r.:l,!ional ,pland1nic blood flow, 111 man Ang1ocrnrhic ,tudie, Acta Ch1r Scand 1980,500(Suppl l l.7 1-1

I 2 Bk1om SR. Moruml'r CH, Thorner MD lnhib1t1nn of g,1'tnn ,rnd g,1,rnc aod ,.:at·uun hy growth hormone rcll'a,t' mh1h11ing horn1<HW L:1nce1 19i9 .11. I 106-ll

I~ Cartl'r RE, H11ar KN, Al,1,, AM, MakhloufGM. lnh 1h111rn1 ,,r VIP,umu lawd 1nt,·,un,1l ,cnct1<1n ,ind cv,li l" A1'. 11' prnducnnn hv '"m,11",wun 1n thc· rat Ga,troentl'rok,gv ll)78.74 726-10

14 Gu:111d;1lini S. Kachm JF, Smirh Pl . F1L'ld M In \'itm l'ffen, pf spmatll,talln on 1,111 tram,porr m rnhb111ntl's1i1w Am J Phv~H,I 1980:2 ~8 G67 74

15 Dharmasarhaphorn K. Racu,t'll L. Bmder HI. D<,bhms JW Somawst,1t1n ,umulatcd ,odium ch lomfr .1h,<>rpttPn 111 the rnhhn ileum Ga,tro,·11t,·n,k,gy llJ80,7K l'i59-6'i

16 Dh,mna,athaphllrn K. Sherwm RS. Dohhin, JW S0maw,1.1t111 mh1b11, ilu1d ,ecr.:tion in the rat JCJUnum G,ts1n1rntcmlogv 1980.7K 1554-8

17 [)h,1rm;1smhaphurn K. R,KU,t'n l. .

80

Dohb111, JW Effec1 of somawsraun nn 10n nan,pon 111 the rat n,k,n J Clin

I 11\'c,1 1980,M:8 I 1-20. 18 Bra:eau P. Vale \V, Burgu~ R. ct al

Hypothal,11111c polypepudl' th.it 111h1bns thc• ,ccrcti,111 nf i111111un,1rcacrivc' p1tu1tary gwwrh hnrmn,w Sc1.:ncc 197>. 170 77-9

19 Ruskc,n,· A. Rene E. Chavvi,11lc)A Effect ol somatostann on diarrhea ,m<l 011 ,mall 1nt,·,t mal warcr :mJ el.:ctrolytc trnn,p1ll t in a patient with pancrealll chnkra. Ott.{ Di, ~ci 1982.27 459 o6

2l1 Qua1ri1111'.1. Basil1,c11 G, Conte D, Born1111 A, Bardclla MT. B1nnch1 PA Effl'ct, of sc,matosraun 1nfuston m ftiur pancnt, wah m,il1gnant carc1no1d syndrome Am J Ga,trocntcwl 1983.78 149-51

Z I. Da\'1, GR, Camp RC. Rask111 P, Kreis OJ. Ffr.:ct t1f som,noswtm 1nfus1t1n on Jl'Juna l water and l'lcctmlyre tran:,pon 111 a p,lttl'lll ,, 1th secretory diarrhea due to carc1notd ,yndroml' Ga,tm· c·nterology 198(1;78 H6-9

22 Dharma,athaphorn K. Sherwin RS. Cara land S,Jaffe B. Dohbm,J S1,maro,tal1n mh1h11, dtarrhl'il Ill thc• car11101d s\ndronw Ann lntl'rn ~kd 1%0:92.68-9

23 Kvol, LK. Moerr.:1 CG. O'Conrwll MJ Tr,•,11111cnr nf1he malif.!nant carc11101d ,yndn1mc N rngl J Med 1986. 315.66 3-6

24 Kvol, LK. Buck M. \ loencl C'G. c1 al Treatment of met,hl,\llc 1,kt cc·ll carcino1n.1 with a s(,mtlt<lstaun analt1guc

!"MS 101-995) Ann lnrern ML'd 19H7, IL17 lh2-K

l'i Molla AM. Gyr K. Bardhan PK, Molla A Effect of intravcnou, somato,raun on ~wol output 111 diarrhea due w nbrio cholera Gm,rrocn terology 19R4:87 :84 5-7

26 Dharmasathaphc,rn K. Gorel1rk F". Sherwin RS. CatalnnJ S. Dobbin, J\\' Somato:..taun decrease, d1arrh.:a 111

patients \\ith short-bowel syndrome J Clm Ga,··ocnt.:rol 1%2:4-521-4

27 Bauer W. Bnnl'r U. Docpfnl'r \V, ct al SMS 201 -995 A \'erv p,nent and sclccnvc ocwpl'plldc ,rnalogue o l ,omatostatin with prolongl'd action L1fl' Su 191'2. 11 11, 3-40

21-> L1mher1, SW, Uttcrlmdcn r. Zu 1dcrw1jkJ. VNkum I. NL'ufdd M. Del l\1:0 E Tlw l·ffc,t, of ,1 long·,1Cllng ,nm.1tostat1n analogu,· on growth hormn,w secrl'llon 111 rat and man In Lahril' F. cd 7th lnternauonal Congrl':,s ,,f l:.nd,1cnnolt1gv Amsterdam l:.xet.'rpta l-.bl1ca. 19841-\47

29 Rnhl'rt, WG. Fc<lorak RN. Chang EB In vitn1 dfoc:t, of till' lnng :1C1ing s!lm,Hnstarm ,malngue St-.1S 201-99'i on .:lectwlvt.: 1ran,port hy the rabhn ill'um Gastn><'ntcrnlngy 1988,9,t 114 i-5ll

,,, Edward, C. Cann PA. R.:.id NW. Hold,worth ('[) Effect c1f T\I'(' 11l'\\

anti,,•crctorv drug, 1111 lhnd and

clec1rolvr,• transport 111 a pauent wirh ,ecrctory d1arrh.:a Gut 1986 27 5Kl-6

> l K!l.:I: A. Kra,•n:1111 M. (~yr K l'I al E,capc of thc• rc,pon,c· to a lnni.: ,Kling ,omaro,1.11in analllguc ISMS 201-9951111 pancnts \\'1th VIP\1ma G;1,rro,•nr,·n,logv 1987;92 52i-"ll

H Eriksson B. Ohcri.: K. Andn"<1n T. Lundq\ 1,t G, \\'idc L, WilanJer t Trcatmen1 nf 111al1gnnnr cndocrnw pancre,Hic tum,,r, \\'ith ,1 llC\\

k,ngeacung ,ommnstaun nnalngue, SMS 20t-l)9'i Srand J Ga,tnil'ntcrnl 1981',2 Vi08- 12

B Snuquet JC. S,1ssol,1, Ci. h,richon). Champct1,·r I', Partcn,ky C Ch,1vv1allc· IA Cl111iral and hormonal effl'crs nf a li,ng-,1cting ,,1m;1t1l'it,1t111 analogul' m pannentK endocrine 1umour, and 111 carc1nl>1J ,ynJronw Cann:r 1987.59 16'i4-60

l4 \/1111k Al. T,;.11 :,T, Mnau.iri AR. Chl'ung P. Eck h;i u,er FE '1rn11,11mrat1 n an,, lnguc tSMS 201-995) 111 tlw management nf ga,1n1.:nll'ropancr.:,111c wmours and d1,1rrh\>C:1 ,yndmm,·, Am J lvkd 198(1.81 2) 40

15 Gc.:lhucd G\\'. Bass BL. Men: "l. Becker KL. S<1111acn,rat111 .inalog Eff,,cis on hyp.:rga,rnn,·m 1i1 ,rn<l hypcrra lrnunmem1a Surger1• 198(1, 100 962-70

16 W11l1nrn, G, Andcr,un JV. William, SJ Blood SR. Cl1111cal t'\'alua11on ofSMS WI-995 Long t.:rm tre:nmcnt in gut ncun1.:ndocnnc wmour,, efficary ,,f oral admin1strauon. and poss1hll' usc II\ nc,n-tumoural rn,1ppropnall' TSH hypcrsl·crenon Acta Endocnnol lll87.Z861S11ppl1.l6-16.

,7 "mith SS. Shulm,rn DI. ODom1n TM. ct al Watery diarrhl'a hvp,,kalcm1a. achlorhvdna syndrome 111 an infom Effec1 oi the.: long-acrmg ,!lmm,is1aun :rnaloguc SMS 201 995 <•n rhc disease and lincar growth J Pediatr Ga,trocntcwl Nurr 1987 ;6· 710-6

18 "an tangelo WC. O'Domio TM. K1111 JG, Seven no G. K rcjs OJ Pancrl'atic cholera ,yndromc Effect of a synth,'t1c somato~tatin analog on intl'sunal water

and 1011 transport. Ann Intern Med 198'i .10'\ ,6Vi

W W<1od SM. Kracn:lin /\IE . Adrian TE. Bloom SR Treatment of p;1t1l'llls \\'ith pancreatic cndncmw rumours using~ Ill'\\' long-ncnng ,omato,tat in :-inalogue sympmmatic and peptidl' r.:,pluise, Gut 1985,lt, 4 ~8 44

40. Mat<1n PN, O'Dom11> TM. Howl' BA et al Effect of a long ,Kring ,omato,tatin ;111alogue ISMS 201-lJlJ5) 111,1 pat1e11t with pannem1c chol,·r:i N E:ngl J 1'kd L98'i. ll2 17-21

4 1 Kr;wn:lin ME:. Cheung .J L. \\\,od '-,M. Cm DH, Bloom SR. Lting term tre~rment of ;1 VIPnma \\'1th

,om,11osra1in ,inalogu<' resu lting 111 remi~st,111 nl ,ymptnm, ,md pn,:,ihll'

,hnnk.1gl' ul flll·ta,ta,l'' ( ,a,trl>· cntl·n,1, g\ J<h1.'>'> 1-..5 ,

42 K ,·,11, I K 1'h·ra,r,111c carnnrnd rt1n1<>rs ,ind rh, c,mnu1,l ,vndr,1nw A wk, tl\'l' r.:,·1,'\\ of ch,•muthl·r,1pv .111d hormonal therapy Am I t-.kd 19',(,,'\l 49-'i,

43 Kn,1, Kl . \lo.-rtl'I CCi. o·conntll \IJ. ::i,huu i\J , Ruh1nJ H.ihn RG Trt·,1m1,·nt ,,t tlw m,illl!rl,lnl ,.ir,1n,,1d ,vndrnnw b·,1lu,H1<m ,>f .1 lung-.1,nng ,<1m,11<1,1,H1n ,1nal.,guc ~ l::ngl I \kd l'IM,, ll'i N>l (>

H Kcl'l111g ( 'A B.1w, I\' loduw· l l l \IIB(i up1.1k, 111111, 1.1,t,llr, mcdullaf\ ,.m:11wm,1 ut rh.: dwn11d A pa11c111 trc,Hnl \\'llh "'mnt,ht,lltn ( Jin '\ucl \hJ Jl}t,,', J \ 2(>L~- \

·15 krkm, T\\ .... Kb H'-, 011',mll> r,1. Tunl, " ...;,,l,,111<111 ":-, \l,·,lullar\ ,ar,111<1111.1 ,,f rhc rhvn,1d p,10,r,·.111,· n,·,1J 1uhl.1,1,N, ,1 nd m 1u,,.1d,·n,"1' and p,rn,r,·,Hte p,,lyp<"pr1dc hyp,·r,,·, 1<"11,>n -\ ne\\' ;1,s1,uat1,m .111,l .:l1111,.1l ,111<.I h<>rm, ,n.11 re,pun-.•, to lllng ,1C1111g

,<1m,1to,rann an.11,,g ,\I', 2t~i-•N'i J C:1111 I nJ,,rnn.,I \ !c•tah i'.h 7 ,M 11 l).l}

40 I cd<>rak Ri\' Allen SI E:tf,·ct ,,t "1ma1,"1.111n .111,1l, 1g ( S\ IS .!l~i -<N'i 1,m 1n ,·1, <> mte,11n.1I fluid rrnn,port 1n rat, ,\ l11n1tl'll ,v,renm dkc1 D11! D1, ~c1 (in pn'" I

47 ( <><.>p,·r JC. \\'1ll1a111, :-.:~. K111g RI B.1rkt•r \ IC Ukets of .1 lon).i·a, 1111g '"m~ll.,l,t,111n .rn,ilugtK 111 p.ll1,·nts w11h ,,·,er, 1lt-11't11111\ d1arrhe.1 Br I "urg l'IKb,71121"1 ll

4'> kd11r.1k R1' '-h,·rh.1n1uk R\\ Ah,en,, 111 dfrc1 of ,oma1,"ta11n analul!lll' ('iM'-, 2t)J.lJlJ'i Im d1arrhl',I ·''"''1,H,·d "llh mtlammarory hu\\'el d1,l',bt C,111 J Cia,1m,·1Herul J<)[N, l

49 Hun:1kl'r l ', \ Sup,·ru Furg., A Zachm;mn M Del PP:,, l. ',}rnwrl111l! [) , Pradl'r r\ . l::!t,·ch ,,t th~ long adm!,! ,um,ll,"t,llm ,1nalugu,· ::,M'-, .ll.)J .l)l)=j 111 an mt.mt \I nh mtr,1, t.1hlt d1arrh,,,·,1 I kh Pal'dl,llr Acta 19h1',-! l ll~"\.l)

5,) Jan"\\' Biller I G1t·c·g ~ () DPris10 T Grnnd R ~uc,l'sslul m:atnwnt of id,•opathtC 'l'l'l'<'l<'r\' diarrlw,1 ,1t 111l,1tK\ \I 11h r!w ,om;ll<1sl,lllll ,m,dugu, S\IS 2l1i-995 C.1,trol'ntn,,log1 Jl)i,I', l)4 J~l) l) \

51 Rllhmst•n El\ Jr. fog,·! R S\b 1l~I 995, a ,om,H, isr.11111 ,111:ilogue. ,lllll d 1a rrhl'a Ill tlw .llqu1re,l 1mmu11od,,f1n,·11L\ ,yndmml' tAIDSI /\1111 lmnn /,.kd 19ti1' l1'll 61'1' I I L,·ttt'rl

52 J..:.n; \ IL). h,tad Bl , Ro,l' C Trl'allnl'nl , ,f "'' ,·r,• ~n J'h "l'"ndiu m·n·lac,·,1 d1arrho,·a \\ 11h ,x:1r<'<ll1d,· Ill ,1 J':llll'l11 \\'1th A.IDS [)rug lntl'il Cl111 l'h.1r111 1%ti!2 l"\-J(,

5 \ Cuok [)I. Kl'li111J<; , S1,1111,: AM C,,11111, '-,~I S<1l11,lh1't,llll) rr,·.nmt'lll tur , rvpto,pond1,1I dr.111 hl'a 111 .1 p,ll1,·111 "11h dw ,1Cqu1r,·ll 1mmun,,d,·ti.:1c1h·,

,yndruml lAl[)SI A1111 ln1ern \kd J%S.J0'> 101'9

:;4 Mulkr ~It-.: Breul'r NI. llal:l'1 J..: Ci11,·hdl H Trearnw111,,t ,·hr,,111l nn11-,l'cr,·1,>r\ d1,1rrhl'a 111 1lco,tt>n1\' ,1·11h the l<111g·,1,nng ,pm,llt1't.ltm ,maJpg <;\ts 2l'I .l)l)'i l Ga•,tr,wmen,I l<.l'>t-.26 IN>-~

'>'i \\ dli.1m, ,._, Cnllpcr JC Ax,,n AT, K111g RI. ll.1rker M l I,,.. lit ,1 lung-arnng ",m,H,"t,11111 an,, 1, ,gu,· Ill c, int r,,llm).i ht, thrl',Ht·nmi,: iil't1'tlltl1\' ,li.1rrhuva Br Mo:d l 1Cl111 R,·,I 1<>,-1 . .!hll ll'2'i-1'

,1, Dud! R_I , -\n,kr",n [)~ h,r,\'rlw AB, 71l'glcr :,...1(; ODons10 T ~ 1 Tr,•atnwnt of d11lwt1, ,l1arrhca ,rnd orrh<1,t,mc hvp,>tl'11'1011 w1th ,om,11 .. ,1.H111 .1n,1l<>gu,· -..,1.., 2l'i 'N'i t\m I ~kd Jl)'-,j',,\ 5"-1 ·.,..,

1 / \ l.1gl1l1'Sllll I, lh1 l' T, 1t,h,111"lll1 l , "lli;:">11 l ' T,,rngr,·n :, , l '\'11.ts .\1.,lwrc K R.111,l, ,m 1,t·d ,luu hi,· blmd m., I 11! ">llll\.tlt.hf,Hlll Ill thl' trt'dlllll'IH (.lf rn., ... ,1\·1.

upp,•r l!,1,tr,,mr,·,tm.1! h.1l'111,,rrhai:, Gui J9ti'i,2o 221 <,

5.'-, \\, rmann B, Kur.. K 011,·n1,111n R T1,·,llm,·n1 uf r,·l,1p,mg hlt·,·d111g PL'J'tlc uk, r-, \\'llh ch,· ,t>n1ill<"t,ll111 ,1n,1lni:u,· S\IS ll~I <N5 111 ,l patl<'IH 1, llh Z1,ll111ger I lbon ,\'ndn>tnl' Hrp,1r., /,!il'lrlll'l1tL'f<llog\' ]l)~) , 12 112• l

~\) Chn,11an-.·11 J, Yut1' t\ The ruk· ul ,um,ll<1't,llll1 ,111d .1 lung ,ll.rlllJ.!

,111,1lugu,, S\.I!::, 2l)J .l)l)'i , Ill ,llllll' hll'l•,lmg du, tn p, pt1,· ukl•ra11,1n '-,,ind _I t,,1,tr<1,·111,·wl J<)'i(,. IJlJ il1l} H

ht1 Palll:,ch J..:[), Sd1uler H '-d1wl'd,•, L' , U,,1del KH l'n11<·,11,,r1 ,ll!,1111,t du<>dt'nal ukl'ratu,n hi' ,um.Hu,1,1t111, Kim \\'t,ch,·11,,hr 19"1(,,t,4 \) \.(1

61 C.1111hna RP :,..:l'\ illl· R Ballantvne ( iH, t'l ,11 S0111,llo,t;i11n and .11nluf.!, I.Kk ,plan,h111, ,·,1s,,ru1btr1Cll\'l l'lf,·ci- 111 ,l11al·,the11:,·d pig, J '-urf.! R,•, 19'>7 .4 1 4'\1,9

62 \\',rng X\1 Tr,·,h.unJI C,,n).i1L1 M. Cnghlan JI' ""'!:f.!111' HA S, ,m,ll,"t,1t1n <'<'ntralh 111h1hn, ,·,1supn·"111 '<'t'retu111 during h,1l'morrhagl' Hr.1111 Rl', l9s7 -rn, 1,N, 2l',

b 3 J..:onrurt·k SJ R1lski J. Ja\\'urek J, T.1sl,•r J. ~ch,,lh A\' Cump,1r,1011 of "'m,Ho,t,ll111 ,md n, h1ghh po1,·1ll hl',n· and <1tt,1pept1d,· .1n,1lui.:, on ,.,,,.-r111l' .tnd ,·ndncnnl' p,111cr,·ari.: "'cr,·11011 Pn,, S,,, hp Bml \.bl 1%,'i Js7 241-9

(,4 Ahn·n B, Tr,mhl·rg !((, B,·n).imark '-, Tre,llm,·nt nl p,lllt'rl',Hl< fi,rula \\'llh t!w "'m,H,hl,Hm an,il .. i.:u,· S\!', 21'1 <N'i Br_! Surg 1988:75 718.

01 <ll'B,,1, \1H B,"111.111 CH d,{,r.1at I', , anl lc1t,).!l'11hu11~< J Cl<>,un· ,>I ;1 h1ch 11uq 11 ''"•·rnal p,1mrt·,111l 11,rul.1 h S\l!::,21)] .l)lJ'i ,1J,,ng-a,11nganal,1guc ut ,,nnat<>,t,llin 1':,·rh J ~kd J%s ,l2 .2,1\ .7

M, P1111 • RA 1'1l kit-man I 11,,ttm,m JI' Tn·.11111l'11 t ut r,111, r, ,111, c Ulollll'llll,

Somatostalln analogue: Therapeullc potenhol

flstuJ.1, Wllh ,1 ,um,lhl,l,11111 ,l11ai11J.! \mJ Surg Jl}St,,J'i'i ,c,.42

67 Rt1,l•nh,·rl! I l\1fol' I)(; <;rhw,1r1: R. ,·1 al Adm1111,1r.m,•n of ,,,m,lln,r,ll111 ,rnalog ('il\l", l,)J.l)<h) 111 ilw 1r,·,ll111t·n1 llt .1 h:-..tula <-H .. ,,:urrtn\,! .1lh.1r p,11h:rc.-. , ...

1ra1i-pl.1nra11<111 1111,•rtn,·1"'' "1tl1 <.: y,k,spc1ruw 1111 mum isu ppr,'"ll '11

Tran,pl.1111,u1,u1 191'7 .4, ,(,4 t,

(1S I l,•11 Hi\ , Brum1ni.: I IA \'t·1,..-ht111r I A lOl11J',Ht,11n ,1f rh, ,-tt,·c 1, ot 1w11 ,omaro,t.Jlnn .111.1logu,·, 111 .1 p,111,·111 w11h .m t'Xlt rnal p,111< r,-,111, fl,tul.1 1'.111cn .i- l\lM1. I lti1' 'I\~

t,<.) T,.11 c;;T Eckh,llN'r !·F Th11111p,<>11 :,..:\\ . ',rrndcl \\'E, V1111k Al l'n1<1p,•1,111\l' u,,. .,f l,,nl! acting "Hn,ll<1st,H111.1n,il,,v iS\I" 2l'l-99'i1111 p,ll1s·nt, \\'llh ,·11d,,u11w wmnur, nl th,· ).i,1,tru..-ntcrup,111r1,·au, .,,.i, ',urger\ Jl}.,..,(, It\) 7'>1' <)5

'i,) l ,,,dl'l f..:H. Uhnla J..:K. l ,·u,.:h1w1 ll rrt',llll1t 11l tlt ,ll"Utt' pancrt,lllll, \\'llh ,uma1<,st,1tm Rl'sult, ni tlw mu I 11, ,·111u douhlt"-bl111d tr1al (,IJ'h·stmh) Pig D1, s,, 1%5,3ll tJl)2

71 l ,,Kkl Kl I l lurmnn,11 and 11onho1 munal , ,·c,,pr11t,t:11,·, dfccr h~ st>1n,11<1,t,H111, I lorm R,·, ll/tili,29 h 1 'i

72 Rohr n K,·in1 V, l \,1d,•I K H l'rl',·en11nr1 of ,·,p,·n11wn1al panL1l',ll1t1, h, ,,,m,ll,1'1,ll111' Klin \\'o, lwnsdu 1%t>,Ml/l-2

7 l l "'d,·1 Kl l. """k-r I l Rohr G Ku,t,·n-r K, P.1l11i,,h J..:l) c;;,h\\'t'dl', l Cytoprn1,·c11,·, propl'l ll<'' ,,f "'111,ll<>· ,r.mn, Kl111 \\'odwn" hr [llS(1,(,-j 5<l-(, 1

74 1\.1,1,·1 J:S:,J<"nkm, St\, Da~ DW, ,·t ,11. l·tll',r- ol stHnatu,r.ll1n and ,1 long ;trlln~ ,nn,ll,"t,llln .111.1logu,· 011 thl'

J'fl'\l'11lll111,111d trc•,Hnwnr of t'XJ'l'nmcnt.1lh 111duc,·d ,l,tll<' p,m,rc.it1 11,111 ilw rat Hr J ",urg 19K5 72: 1ii2· 5

75 C,m,1.1\' DR. D1um111 Ci, l'r111: RA Th, dt,·ct of ,,,m,11,1't,lll11 ,tnalogut' (S~IS l1~J -lJ<Vi) t1n p,111cr,·a11l hlc",d tlt1\\' ~urg,·r\ J\)~1'. IL1-J 1,~24- >U

7h Dharn1,,11haphurn K. Cion·li,k l '~h,·m111 R'- C:.ual.11\d S Dohh111 I\\ s,,111,1tt1,ta11n d,·ul',1"'' Jiarrhe.1 m p,lll<'nt, w11h ,hurt h,,w,•l ,vndn,111<' J Cl111 ( i,1,tro,·m,·ml l<lt-2.4 521-4

77 Ohlh,,um I'. (,alp .. r111l' RI. Dem,uqu,·, IL. \'l•rgnc, I' \famn C l '•,· ut a l011).(·,1,·1111g S<>111,ll<»t,111n ,111,ilogu,· (<:;\tS l1'J .<N'i I 111 wntroll1111! a s1c111fi.:,111t ile,11 output 111 ,l 5·\'l'ilr·old ~h1ld J P,·d1,llr l ;,Nr,,c•m,·rol ~ urr Jl/K7 ,(,,4(,(, ll)

7ti H,1pm,111 \\'I', \\'nlhl'rrnk RC.i. L.1111,·r, CB. \',111 Ti.lll).!l'rt'n JH Tr,•,1tmc11t ,,f the d11mp111).i ,\'nllron1l' \\ Hh rlw "1111,H11,t;n111 ,inalogu,· Sl\lS 101 <l<h Ann Suri! Jl)'>S 2l17 l'i'i-<1

N l'rrmru,t• )1\ Br,1111ll'V P. !ohn,1011 l) Thl' u,, ,1follrc·ot1dt 1'-M'> 2Lli-ll9'i) 111 rlw cr,·,11ml'lll .,f 111tra,·1ahk dumping .1 I 11.·r , .1gi 1t<.111n l 1r J.!,1,t re1.. tc. Hn\·

(ia,rrn,·111l•r11l"J.!' Jl/S'> ,94 ,\ 11'('1

81

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