MULTI-SHOT METERED DOSE INHALER (MDI) AND RESERVOIR DEVICES. GS Rachelefsky, MD, AR Clark, Bsc, M Goldenhersh, MD, PL Mason, BS, and AM Hollingworth, Los Angeles, CA. Many patients benefit from using MDIs with spacer or reservoir devices. Concomitant therapy with separate MD1 doses of cromolyn sodium and beta-agonist is common practice. If 2 shots from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. We used a Multistage Liquid Impinger (a fourstage inertial impaction device, incorporating a;l inlet bend and an absolute filter, which separates an aerosol cloud into 6 fractions) to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber and an Inspirease. Results are reported by analysing mg of cromolyn sodium per actuation retrieved. With the Aerochamber, 2 shots cromolyn sodium followed by 2 shots albuterol resulted in the total dose to patient being reduced by 75% (0.19 vs. 0.05mg) and the effective dose of fine particle (<6.4um) being reduced by 80% (0.13 vs. O.O3mg), when compared to 2 shots cromolyn sodium alone. Using the Inspirease, total dose was decreased by 80% (0.32 vs. 0.06mg) while the effective dose of fine particle was reduced by 60% (0.13 vs. O.O5mg), when compared to cromolyn sodium alone. The use of cromolyn sodium and albuterol ~~1s in a multi-shot combination with the Aerochamber or the Inspirease is not recommended since this leads to a loss of the dose delivered when compared to single administration.
FEIEDIF'INE IN llNECiD f%Tl'IM. %.R. Patel,+E.peerS and *.T.w. Kerr, '+rqdnmt of Respjram pledicine, !+lbdem InfYmeq, Q.asgv.4, Scotland, and +Astza pfiarrnaceutical Ltd., Kines Langley, W. Felcdipine is answcalciunanmtof the dil'@opyridine grcup. Its vaec&lam activity at mutic ccncentr-aticm is palatably related to interacticn+Fth Ca++ bindhgptejnsra~thanthe inbititicn0fC.a influx acmxss the potential operated channels. We have ex&ned the effect of lm felcdipjne in oral solution cm th? resting ~tortcneandexerciEeinducedfall inFOJland~ina~toccntrolled,douhlehlindranda&& croaz over stdy in 10 mtensive as-tic patients. The FEV was at least 80% of predicted ncu.msl vslLE.IYi2artrat.e 4 ~),BP,FEvl&Fvc~~Izfore snduptojominafteriTJxatm?ntswhsnexercisechsll~ [email protected]
staterlmnjngonatrea&ilatsub-maXillU.~klcedsFEV, k Fvc,HRalxlBpwere recu&datregularintenmlspoeexerciseupto60rrdn.Felodipinedidnotaffectthe'teseline FEY &FE. l-lxever, the exerde rildEed fall in Fhvmdbc ma partially jnbibited with p?Aectial capred b placeko of 63% (~(0.01, Wilcoxcm test). Seven patients [email protected]
patients also felt light headed after exercise. The post tX.Yatnk?ntttendedtobelcn$erandIRhighsranfelcdipins. Fel~pinsisunlikelytolzasuitahledcugin~t of asthm, ht it can be usedsafely to treat12ypertensive patients withco-existingot&ructive~ disease. Tk mean (ml) lrlseline FBI1 , lm and ths llk?sn Ili%chm fallinFEJ$. E?T!dES pcet -%fau 3.10(0.25) 3.10(0.25) 24C4.7) Placebo z1 4.x)(0.31) 4.3NO.35) 17C5.4) Felcdipine FEY 3.XNO.25) 3.30(0.28) 9(4.1) FE1 4.WO.38) 4.40(0.38) 6c3.5)
Leukotrienes (LT) C D andE are the active corqonents of &-A*and ar: important mediators of the pathobiology of bronchial asthma. Sch 37224, l-(1,2-dihydro-4-hydroxy-2oxo-1-phenyl-1,8-naphthyridin-3-yl) pyrrolidinium, hydroxide, inner salt, decreases the release of these LTs during an allergic reaction and at sites of inflamation. This ccmpound inhibits LTD and TxB, release by anaphylactic guinea pig iung (IC = 3.9flfi and 1.9& respectively). Purthe’&re, Sch 37224 (15 mg/kg, p.0.) inhibits the accmulation of LTE and TxB as well as the edema and neutrophif infiltrkm associated with a reverse passive Arthus reaction in the rat pleural cavity. However, the cmpound does not inhibit 5-lipoxygenase, cyclooxygenase or phospholipase 4 in vitro. Sch 37224 decreases (ED,, - 1.3 fl9,p.a.) a LT-mediated allergic bronchospasm in guinea pigs, and at 0.5 mg/kg, p.0. also inhibits hyperventilation-induced bronchoSpaSaa. It is neither a bronchodilator nor a receptor antagonist of histamine, serotonin, methacholine, Ln: or PAF. Sch 37224 is, therefore, a prc&ing new antiallergy agent that inhibits LT release and has the added benefit of exerting antiinflairmatory activity. It is expected to be efficacious not only against the bronchoconstriction, but also against the pulmonary inflammation and hyperSensitivity associated with chronic pulamary diseases such as asthma.