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97 Theo-24 vs. Theodur kinetics using stable isotope methodology
THEO-24 VS. THEODUR KINETICS USING STABLE J. Koup G ISOTOPE METHODOLOGY. S. Walker, Sha iro, W. Howald, W. Pierson C W. Bi&man &&%a. Seattle Washin&.oA To determine the relative bioavailability fF) of a theophylline preparation and intrapatient variation in theophylline clearance 24 hour sampling is necessary as is the use of the stable isotope NI5,7,CI3 theophylline. Twenty children aged 12 or older were randomized in a double-blind steady state crossover study to receive theo 24 once a day and theodur placebo or theodur twice a day and theo 24 placebo. After a 24 hour hospitalization in the research unit, each received the alternate treatment regimen and was rehospitalized one week later. Albuterol was the only adjunctive therapy. Drug kinetic parameters were evaluated. Serum concentration data shows that patients were at steady state during study intervals for both products. The AUC (area under curve) for hour O-12 is significantly greater than AUC for hours 12-24 for both. F, when corrected for clearance of the stable isotope, was .976+.145, range is .71-1.15. The correction produced a significant decrease in variation (p<.D5). Percent variation in plasma concentration between the two drugs were compared. There were no significant differences between the two regimens as measured by pulmonary function values FVC (t=D.60), FEV (t=0.92),FEF 25-75 (t=0.64) and PFER (t=0.36) or by the use of albuterol prior to hospitalization. Once a day theophylline is a useful asthma therapy in adolescents.
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SLOW-RELEASE THEOPHYLLINE INHIBITS THE LATE ASTHMATIC REACTION TO TOLUENDIISOCYANATE IN SENSITIZED SUBJECTS. Crescioli S, Dal Vecchio L, Zocca E, Paleari D, Pozzan M, Mapp C, and Fabbri LM. University of Padova,Italy. To slow-release determine whether asthmatic inhibitis late theophylline the reaction to toluendiisocyanate (TDI), we studied Slow-release six subjects. sensitized theophylline (Theo-Dur 6.5 mg/Kg b.i.d. for 5 days) or placebo were randomly administered in two series of experiments, and the last dose was given one hour before exposure to TDI (0.018 When the subjects were treated min). 30 pm; FEV-1 was markedly decreased at 4 with placebo, and 6 hours after exposure to TDI, and was still reduced at 8 hours. When the subjects were given serum theophylline theophylline, slow-release mcglml for the 8 remained stable at 18.5+1.8 and the decrease in FEV-1 was hour study, significantly inhibited at 4 and 6 hours after exposure (Table). FEV-l(L) after exposure to TDI Treatment Q-hour 6-hour a-hour 0 2.91 3.05 2.95 Theophylline 3.57 2.02 2.53 1.99 Placebo 3.47 c11.02 CO.001 ns ns p value slow-release that suggest results These asthmatic late inhibits the theophylline reaction to TDI.
HYPER EOSINOPHILIA AND RECURRENT'INGlOEDEM.4IN A 2% YEAR OLD GIRL. -----D.R. Katzen '---‘P F_'_--___-Weller and D.Y.M. Leung, Boston, MA. Recently Gleich et al (NE.!M 31~i:16?.1, 1984) described 4 patients with a new s:.ndrome consisting of episodic angioedema and hT,‘oereosinophilia. We wish to report n girl with onset of similar episodes at 2% years of ace. Slrc had episodes every 3-4 weeks of abrupt onset of nonpitting edema of her face, trunk :jnd extremities associated with temperature elevaclons up to 103O, malaise and up to 25X weigh: ga-in followed by the development of pruritic trunk& papules. Pulse prednisone therapy provided ,:ompletr resolution of symptoms within 48 hrq. Marked eosinophilia (up to 56,(X% absolute eosinophil count (AEC)) was consis*rentlp seen during acute episodes with a decrtA,rse during asymptomatic intervals (4,000 AEC>. Evaluation for parasites and malignancy were negative. Complement studies and immunoglobulins G,A,E levels were normal but her IgM level (208 mg X) was increased. Delayed skin tests were absent during acute and asymptomatic intervals. Immune complexes by Cl binding were markedlv elevated at 900 ug/ml (n 9 L23 ug/ml). CxR, EKG, renal and hepatic functions tests were normal. This is the youngest patient reported with this recently described syndrome. Its recognition is important because of the rapid response to pulse steroids and favorable prognosis. The mechanism of this illness is unknown but its cyclical nature and associated immune abnormalities are directing us to further investigate the role of hormonal or immune inf'iui:?:‘e:: on this syndrome.
MEASUREMENT OF CUTANEDUS UaSCUlAR PERNEABICITY. T.M. Keehey, M.D., J. lndrisano, %A. Kaliner, M.D., Bethesda, &ityland. Vascular Dermeabilitv (VP) is central to the pathogenesis'of urticar:a; angioedema, and other In order to study cutaneous allergic phenomenon. VP in rodents, radiolabelled IgG, albumin, and neutral dextran fractions having Stokes-Einstein radii of 35 to 125 angstroms (A) were employed. The time course of VP in response to intradormet injections of histamine, bradykinin, serotonin and immunologically mediated immediate hypersensitivity was studied. Although dose response to mediators varied on a molar basis, VP after all stimuli was similar; peak tracer influx occurred in 15 to 20 min and pore size exceeded 125 A. Furthermore, individual tracers tended to persist in tissue for up to 24 hrs. after peak VP had occurred. Thus, mediators of immediate hypersensitivity reactions all induce vascular pores > 125 A and generate similar UP characteristics. The relationship of late phase reactions (LPR) and VP were examined employing immunologic cutaneous mast cell degranulation. Whereas a marked increase in VP occurred within 30 min, analysis of skin tracer accumulation at 2, 4, 8, and 24 hrs. failed to reveal additional VP. These findings suggest that VP may not be a prominent component of LPR. If these data can be extrapolated to humans, it suggests that cell infiltration and/or compromised lymphatic clearance may be primarily responsible for the clinical induration accompanying LPR.
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SLOW-RELEASE THEOPHYLLINE INHIBITS THE LATE ASTHMATIC REACTION TO TOLUENDIISOCYANATE IN SENSITIZED SUBJECTS. Crescioli S, Dal Vecchio L, Zocca E, Paleari D, Pozzan M, Mapp C, and Fabbri LM. University of Padova,Italy. To slow-release determine whether asthmatic inhibitis late theophylline the reaction to toluendiisocyanate (TDI), we studied Slow-release six subjects. sensitized theophylline (Theo-Dur 6.5 mg/Kg b.i.d. for 5 days) or placebo were randomly administered in two series of experiments, and the last dose was given one hour before exposure to TDI (0.018 When the subjects were treated min). 30 pm; FEV-1 was markedly decreased at 4 with placebo, and 6 hours after exposure to TDI, and was still reduced at 8 hours. When the subjects were given serum theophylline theophylline, slow-release mcglml for the 8 remained stable at 18.5+1.8 and the decrease in FEV-1 was hour study, significantly inhibited at 4 and 6 hours after exposure (Table). FEV-l(L) after exposure to TDI Treatment Q-hour 6-hour a-hour 0 2.91 3.05 2.95 Theophylline 3.57 2.02 2.53 1.99 Placebo 3.47 c11.02 CO.001 ns ns p value slow-release that suggest results These asthmatic late inhibits the theophylline reaction to TDI.
HYPER EOSINOPHILIA AND RECURRENT'INGlOEDEM.4IN A 2% YEAR OLD GIRL. -----D.R. Katzen '---‘P F_'_--___-Weller and D.Y.M. Leung, Boston, MA. Recently Gleich et al (NE.!M 31~i:16?.1, 1984) described 4 patients with a new s:.ndrome consisting of episodic angioedema and hT,‘oereosinophilia. We wish to report n girl with onset of similar episodes at 2% years of ace. Slrc had episodes every 3-4 weeks of abrupt onset of nonpitting edema of her face, trunk :jnd extremities associated with temperature elevaclons up to 103O, malaise and up to 25X weigh: ga-in followed by the development of pruritic trunk& papules. Pulse prednisone therapy provided ,:ompletr resolution of symptoms within 48 hrq. Marked eosinophilia (up to 56,(X% absolute eosinophil count (AEC)) was consis*rentlp seen during acute episodes with a decrtA,rse during asymptomatic intervals (4,000 AEC>. Evaluation for parasites and malignancy were negative. Complement studies and immunoglobulins G,A,E levels were normal but her IgM level (208 mg X) was increased. Delayed skin tests were absent during acute and asymptomatic intervals. Immune complexes by Cl binding were markedlv elevated at 900 ug/ml (n 9 L23 ug/ml). CxR, EKG, renal and hepatic functions tests were normal. This is the youngest patient reported with this recently described syndrome. Its recognition is important because of the rapid response to pulse steroids and favorable prognosis. The mechanism of this illness is unknown but its cyclical nature and associated immune abnormalities are directing us to further investigate the role of hormonal or immune inf'iui:?:‘e:: on this syndrome.
MEASUREMENT OF CUTANEDUS UaSCUlAR PERNEABICITY. T.M. Keehey, M.D., J. lndrisano, %A. Kaliner, M.D., Bethesda, &ityland. Vascular Dermeabilitv (VP) is central to the pathogenesis'of urticar:a; angioedema, and other In order to study cutaneous allergic phenomenon. VP in rodents, radiolabelled IgG, albumin, and neutral dextran fractions having Stokes-Einstein radii of 35 to 125 angstroms (A) were employed. The time course of VP in response to intradormet injections of histamine, bradykinin, serotonin and immunologically mediated immediate hypersensitivity was studied. Although dose response to mediators varied on a molar basis, VP after all stimuli was similar; peak tracer influx occurred in 15 to 20 min and pore size exceeded 125 A. Furthermore, individual tracers tended to persist in tissue for up to 24 hrs. after peak VP had occurred. Thus, mediators of immediate hypersensitivity reactions all induce vascular pores > 125 A and generate similar UP characteristics. The relationship of late phase reactions (LPR) and VP were examined employing immunologic cutaneous mast cell degranulation. Whereas a marked increase in VP occurred within 30 min, analysis of skin tracer accumulation at 2, 4, 8, and 24 hrs. failed to reveal additional VP. These findings suggest that VP may not be a prominent component of LPR. If these data can be extrapolated to humans, it suggests that cell infiltration and/or compromised lymphatic clearance may be primarily responsible for the clinical induration accompanying LPR.
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