Fluticasone propionate in inflatntnatory bowel disease - Hindawi

IBD: TRENDS IN MEDICAL THERAPY

Fluticasone propionate in inflatntnatory bowel disease MARTA CARl'ANI DF. KASKI, MD, HUMPHREY

JF HOL'lGSON, OM, FRCP

ABSTRACT: Although effective for both acute and often long term treatment of inflammatory bowel disease, systemically absorbed corticosteroids have a high incidence of side effects. This article briefly reviews the pharmacokinetics of corticosteroids and the strategics available for reducing systemic side effect~. In rarricular, fluttcasone propionate is a fluorinated glucocorticoid, in which systemic side effects are absent or minimal due to its relatively low absorption and rapu.l first pass metabolism In an open trial in 12 patients with mild and moderately active Crohn's disease, administration of 20 mg fluttcasone pro1,1onate or.1lly was associated with a significant fall in the Crohn's disease activity index and improvement in other parameters of inflammation, without change in either plasma cortisol levels or responsiveness to adrenocorticotropic hormone, suggesting that this drug is a promising therapy fo r Crohn's disease meriting evaluation against conventional corticosteroids. Can J Gastroenterol

1990;4(7):417-419 Key Words: CLnica! tnal, Corticosteroids, Crohn's disease, Fluticasone propionate

Le propionate de fluticasone dans les maladies inflammatoires de l'intestin RESUME: Bien qu'efficaces dans le traitemcnt des maladies inflammatoires de l'intestin - aigues et a long terme, !es corticostero"ides absorbes par voie genera le s'accompagnent d'une incidence elevee d'effets indesirables. Le present article examine rapidement la pharmacocinetique des comcostero"ides ainsi que les strategies permettant de redu ire les effets secondaires systemiques. ll note que le propionate de fluticasone est un glucocortico"ide fluore dont les effets sccondaires sont absents ou minimes en raison de son absorption foible et de son metabolisme rapide de premier passage. Dans un cssai ouvert, 12 patients portcurs d'une maladie de Crohn faiblement ou mcxic'.:rement active ont re~u du propionate de fluticasone oral a la dose de 20 mg. Les resultats - chute significative du CDAI et amelioration des paramecrcs inflammatoires, sans changement des taux plasmatiques de cortisol ou de la reponse a l'ACTH - suggerent que ce medicament pourra1t offrir un remede prometteur a la maladie de Crohn et qu'il merite d'etre evalue par rapport aux corticostero"ides conventionnels. Royal Pos&graduace Medical School, Hammersmith Hospira!, London, United Kingdom Correspondence and reprints: Dr M Carpani de Kask1, Royal Poscgraduace Medical School, Hammersmith Hosprral, London, United Kingdom WI 2 OH5. Telephone (081) 743-2030 CAN

J GA~TROENTEROL VOL 4 No 7 NOVEMBER 1990

C

ORTICOSTEROIDS ARE Tl IE MOST

effective smgle class of drugs available for the treatment of inflammatory bowel disease (IBO). In conrrolled therapeutic tnals they have been demonstrated to be effective m the creatment of acute ulcerative col1t1s and active Crohn's disease (I). They are more effective than salazopyrine and similar drugs m th e treatment of active colonic Crohn's disease ( 1,2), and it 1s only m mild cases of ulcerative colttis that 1t appears that 5-ammo~al icylate therapy may be as effective. ln addition ro their undoubted efficacy in treating active disease, corticosteroids play a substantial role in mamtainmg remission or suppressing disease activity long term. Whi le m ulcerative coitus this 1s resorted to only rarely, a substantial proportion of patients wirh Crohn's disease who enter rem1ss1on on steroid therapy become steroid-dependent (2). There is controlled evidence of the value of low Jose steroid therapy (8 mg mechylpredmsolone per day) in maintaming remission in such patients (2). This beneficial effect is however undoubtedly achieved at the pnce of considerable side effects. In the mulu-

cencre National Cooperative Crohn's Disease study (3), prednisolone given orally (0.05 to 0.75 mg/kg body weight) for 17 weeks caused obvious side effects (moon face, acne, ecchymos1s, hyper417

CARPANI m KASKI ANn I IOLX,~ON

tension) in over 50% of patients when used lo treat active disease. Side effects were seen in approximately nne-third of patients when lower doses were used in an attempt to maintain remission (0.25 mg/kg body weight). Long term admmistration of prednisolone also resulted in a significant rise in blood leukocytes and hematocrit values. A more recent study evaluated the incidence of osteoporosis in patients with IBD and reported that 30% of the patients studied were osteoporotic ( 4). Those at highest risk were patients with longstanding, severe small intestinal disease; those with intestinal resection, secondary amenorrhea or premature menopause; and those on high dose steroid therapy. There was a clear negative correlation between lifetime steroid dose and bone mineral content. Another study reported that 4.3% of patients treated with corticosteroids for IBD over a IO year period developed osteonecrosis (5). Side effects are seen both with enemas and with oral or intravenous therapy. In mild disease, enemas have been shown to be more efficient than systemic steroids if the effect is telated to the plasma cortisol achieved (6). This in itself 1s not surprising. Unfortunately, it is not possible to limit corticosteroid therapy co local use, as local enema a1d with no system ic gl ucocorticoid effect after oral, intrarecral, and inrranasal applicar1on. C lm Pharmacol Ther 1983;22:343-50. Lcvinwn RA. lntrarectal treatment of ulcerative col itis with tixocortol pivalate, u topical no nsystemic anti-inflammawry Hermd, comparison with h yd rocorusone enema. Gastroenrcrology 1986;90: 1520. Hanauer SB. C linical experience with tixocortol p1valate. Can J Gamocnterol 1988;2: I 56-8. Mitchison H, Al Mardini I I, Zaitoun A, Record CO. Beneficial effects of the cnpical steroid fluncasone proprionate in uncreated cocliac disease. G ut 1989; 30:Al451. Carpani M, Peters AM, Hodgson HJF, et al. Q uant ificat ion of whole body granulocyte excretion inflammatory bowel d1~ease. N ucl Med Comm 1989;10:267. Carparn Jc Kask1 M, Pete" AM, Lavender JP, c1 al. Oral fluticasonc propionate m active Crohn 's disease. Gut 1989;30:Al480.

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