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1.
Pharmacotherapy ; 19(11): 1243-51, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10555930

RESUMO

STUDY OBJECTIVE: To evaluate the effect of a potent experimental leukotriene receptor antagonist, MK-571, on airway responses to inhaled allergen. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Clinical research center. SUBJECTS: Eight male volunteers with allergic asthma. INTERVENTIONS: An intravenous loading dose was followed by an 8-hour infusion of MK-571 or placebo, with a 7- to 14-day washout between treatments. Allergen challenge was performed after the loading dose and a histamine challenge was performed before and 24 hours after allergen. MEASUREMENTS AND MAIN RESULTS: Forced expiratory volume in 1 second was measured serially. MK-571 provided about 50% protection during maximum early and late responses compared with placebo (p=0.005), but airway obstruction persisted 8-24 hours after allergen on both treatment days. Airway responsiveness to histamine was not significantly attenuated at 24 hours. CONCLUSION: Blocking Cys LT1 receptors for 8 hours attenuated the early and late responses but did not interrupt the cascade of events leading to subsequent allergen-induced airway obstruction and hyperreactivity.


Assuntos
Obstrução das Vias Respiratórias/prevenção & controle , Alérgenos/imunologia , Hiper-Reatividade Brônquica/prevenção & controle , Cisteína/antagonistas & inibidores , Antagonistas de Leucotrienos/farmacologia , Leucotrienos , Propionatos/farmacologia , Quinolinas/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino
2.
Eur Respir J ; 14(1): 12-8, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10489822

RESUMO

Leukotrienes are pro-inflammatory mediators which may contribute to tissue, sputum, and blood eosinophilia seen in allergic and inflammatory diseases, including asthma. Montelukast is a cysteinyl leukotriene1 (CysLT1) receptor antagonist which improves asthma control; the aim of this study was to investigate its effect on induced sputum eosinophils. Montelukast 10 mg (n=19) or placebo (n=21) were administered orally once in the evening for 4 weeks to 40 chronic adult asthmatic patients, aged 19-64 yrs, in a double-blind, randomized, parallel group study. Patients were included if, at prestudy, they had >5% sputum eosinophils, symptomatic asthma with a forced expiratory volume in one second > or =65% of the predicted value and were being treated only with "as needed" inhaled beta2-agonists. In addition to sputum eosinophils, blood eosinophils and clinical endpoints were also assessed. Four weeks of montelukast treatment decreased sputum eosinophils from 7.5% to 3.9% (3.6% decrease, 95% confidence interval (CI) -16.6-0.4). In contrast, placebo treatment was associated with an increase in sputum eosinophils from 14.5% to 17.9% (3.4% increase, 95% CI -3.5-9.8). The least squares mean difference between groups (-11.3%, 95% CI -21.1-(-1.4)) was significant (p=0.026). Compared with placebo, montelukast significantly reduced blood eosinophils (p=0.009), asthma symptoms (p=0.001) and beta2-agonist use (p<0.001) while significantly increasing morning peak expiratory flow (p=0.001). Montelukast was generally well tolerated in this study, with a safety profile similar to the placebo. These results demonstrate that montelukast decreases airway eosinophilic inflammation in addition to improving clinical parameters. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.


Assuntos
Acetatos/uso terapêutico , Asma/tratamento farmacológico , Antagonistas de Leucotrienos/uso terapêutico , Eosinofilia Pulmonar/tratamento farmacológico , Quinolinas/uso terapêutico , Doenças Respiratórias/tratamento farmacológico , Adulto , Asma/complicações , Asma/fisiopatologia , Ciclopropanos , Método Duplo-Cego , Eosinófilos/efeitos dos fármacos , Feminino , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Eosinofilia Pulmonar/complicações , Eosinofilia Pulmonar/fisiopatologia , Testes de Função Respiratória , Doenças Respiratórias/complicações , Doenças Respiratórias/patologia , Segurança , Escarro/citologia , Escarro/efeitos dos fármacos , Sulfetos , Resultado do Tratamento
3.
Thorax ; 52(12): 1030-5, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9516894

RESUMO

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis. RESULTS: The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction. CONCLUSIONS: Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.


Assuntos
Acetatos/uso terapêutico , Asma Induzida por Exercício/tratamento farmacológico , Exercício Físico/fisiologia , Antagonistas de Leucotrienos , Leucotrieno E4/urina , Quinolinas/uso terapêutico , Acetatos/sangue , Adolescente , Adulto , Asma Induzida por Exercício/sangue , Asma Induzida por Exercício/urina , Estudos Cross-Over , Ciclopropanos , Método Duplo-Cego , Teste de Esforço , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/sangue , Sulfetos
4.
J Clin Pharmacol ; 34(2): 158-66, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8163716

RESUMO

Improving protein and fat absorption in patients with cystic fibrosis relates to the amount of biologically active enzyme reaching the duodenum. Microencapsulated formulations are more effective than conventional products but differ in content, ability to retard acid inactivation and the pH at which they release enzymes. Contaminants in these products contribute to hyperuricosuria.


Assuntos
Fibrose Cística/tratamento farmacológico , Insuficiência Pancreática Exócrina/tratamento farmacológico , Pancreatina/uso terapêutico , Adolescente , Química Farmacêutica , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/fisiopatologia , Humanos , Absorção Intestinal , Lipase/metabolismo , Microesferas , Pâncreas/enzimologia , Pâncreas/fisiopatologia , Pancreatina/administração & dosagem , Pancreatina/farmacologia
5.
JAMA ; 263(18): 2459-61, 1990 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-2329633

RESUMO

Pancreatic enzyme products are formulated, manufactured, and sold without submitting efficacy or bioavailability data to the Food and Drug Administration because of a quirk in the law. We documented therapeutic failures in three patients with cystic fibrosis after pharmacists substituted generic pancrelipase capsules for the Pancrease brand. Gastrointestinal symptoms and fat malabsorption rapidly resolved after therapy was reinstituted with brand name products. In vitro analysis indicated that after 1 hour of exposure to simulated gastric fluid, lipase activity was less than 200 U per capsule from all three generic capsules dispensed to the patients compared with 6820 U per capsule from Pancrease. These data indicate that the enteric coating of the generic product was defective and that the substituted product was not bioequivalent to the prescribed brand. We conclude that the Food and Drug Administration should institute regulations over this group of products.


Assuntos
Fibrose Cística/tratamento farmacológico , Lipase/efeitos adversos , Lipase/metabolismo , Extratos Pancreáticos/efeitos adversos , Equivalência Terapêutica , Adulto , Cápsulas , Criança , Feminino , Humanos , Lactente , Masculino , Extratos Pancreáticos/metabolismo , Pancrelipase , Padrões de Referência
6.
J Pediatr Gastroenterol Nutr ; 8(3): 404-7, 1989 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2709273

RESUMO

A 14-year-old boy experienced multiple hospitalizations because of symptoms due to Crohn's disease involving the stomach, duodenum, and ileum. He maintained that oral corticosteroids were not effective for control of his symptoms. However, i.v. corticosteroids always relieved his symptoms. To resolve the question of noncompliance versus altered corticosteroid absorption or metabolism, our patient underwent an oral prednisone absorption study. Prednisolone, the active metabolite of prednisone, was measured in his plasma using a high-pressure liquid chromatography technique. The results led to the discovery of an elaborate deception by the patient and his subsequent need for psychotherapy. This report documents the importance of measuring plasma prednisolone concentrations to diagnose noncompliance, especially in adolescents who are overly concerned about their body image.


Assuntos
Imagem Corporal , Doença de Crohn/tratamento farmacológico , Cooperação do Paciente , Prednisolona/sangue , Prednisona/uso terapêutico , Adolescente , Humanos , Masculino , Prednisolona/farmacocinética
7.
Clin Pharm ; 7(5): 391-7, 1988 May.
Artigo em Inglês | MEDLINE | ID: mdl-3383545

RESUMO

A case of long-term acetaminophen overdosage in a six-year-old child, which contributed to her death despite optimal medical management including oral acetylcysteine therapy, is reported. Acetaminophen 325 mg every six hours was prescribed for fever associated with measles. Believing that acetaminophen was nontoxic, the child's mother progressively increased the dose over three days, first in response to fever and subsequently for abdominal pain probably secondary to unrecognized acetaminophen toxicity. On admission to the hospital, the patient's serum acetaminophen concentration was 163 micrograms/mL (11 hours after the last dose); subsequently, the acetaminophen half-life was determined to be 15 hours. A course of oral acetylcysteine therapy (a loading dose of 140 mg/kg as the sodium salt followed by 70 mg/kg every four hours for 17 doses) was begun. Hepatic and renal failure developed within two days, followed by the onset of seizures, and brain death occurred on the 11th day. Autopsy findings consistent with acetaminophen toxicity included centrilobular hepatic and renal tubular necrosis. Aspergillis fumigatus and Cryptococcus neoformans isolates from pulmonary abscesses and bronchopulmonary lymph nodes, respectively, were an unexpected finding. However, in the absence of acetaminophen overdosage, death would have been unlikely. Cryptococcal lymphadenitis was believed to have been the initial febrile illness that was treated with supratherapeutic doses of acetaminophen. Fatalities in children from a single overdose of acetaminophen have been rare, and there is only one previous report of a fatality after long-term administration of multiple excessive doses. The lethal outcome in this case illustrates the need to educate the public on the potential toxicity of nonprescription medications.


Assuntos
Acetaminofen/intoxicação , Acetaminofen/sangue , Acetilcisteína/uso terapêutico , Alanina Transaminase/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Criança , Feminino , Humanos , Tamanho do Órgão/efeitos dos fármacos , Diálise Renal
8.
J Orthop Res ; 6(3): 311-6, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3357081

RESUMO

Preoperative antibiotics are an important measure taken to prevent infection in joint replacement surgery. The local availability of these antibiotics in the operative site is absolutely necessary to ensure adequate prophylaxis against contaminant bacteria. Because pulsatile-lavage rapid-recovery systems have become a routine technique of bone preparation in joint reconstruction, we chose to study the effect of these systems on local antibiotic concentrations. We further investigated the effect of irrigation with and without use of a limb tourniquet. For our study, we obtained 23 bone specimens in 16 patients undergoing joint reconstruction (14) or amputation (2). The patients were classified into one of four groups based on whether a tourniquet was applied during the procedure and whether the bone specimens were irrigated. In addition, matched blood samples were obtained to establish that therapeutic serum levels were achieved. Nine patients contributed 13 bone specimens, which underwent vigorous irrigation in vitro. None of these specimens had detectable levels of antibiotics, regardless of whether a tourniquet was used. Seven patients yielded 10 bone specimens, which were not irrigated. Five of these seven patients had detectable levels of antibiotics. In addition, the specimens from limbs without tourniquets had levels that averaged 0.51 microgram/ml while those with tourniquets averaged below 0.2 microgram/ml. Therefore, the use of vigorous irrigation in bone preparation has a significant deleterious effect on the local presence of previously administered systemic antibiotics. This effect is compounded if the operative site is isolated from continuous blood flow by use of a tourniquet. We therefore recommend that additional measures be taken to ensure that adequate antibiotic levels are present.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Antibacterianos/uso terapêutico , Osso e Ossos/análise , Irrigação Terapêutica , Torniquetes , Idoso , Aminoglicosídeos , Antibacterianos/sangue , Humanos , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/prevenção & controle
9.
J Pediatr ; 110(2): 303-10, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3806307

RESUMO

Gentamicin serum concentrations were measured in 15 children and seven adults with cystic fibrosis and in eight children with other diseases. Potentially toxic trough concentrations occurred in three of the first nine patients studied, in whom the dose and a 4-hour dosing interval were prescribed on the basis of one-compartment pharmacokinetic calculations (Sawchuck-Zaske method). In contrast, final concentrations were within the accepted target ranges for the remaining 13 patients with cystic fibrosis, in whom the dose and interval were adjusted empirically on the basis of a single pair of "peak" and trough values. The mean +/- SD final dosage required to achieve target concentrations was 13.8 +/- 2.9 mg/kg/d for children and 11.8 +/- 1.1 mg/kg/d for adults (P greater than 0.05), generally divided into four doses at 6-hour intervals. Mean half-life and incremental increase in serum concentration from previous trough to subsequent "peak," an indirect measurement of volume of distribution, were not significantly different between children or adults with cystic fibrosis and pediatric control subjects; there was little interpatient variability in these values. Thus the high dosage requirements were related more to the higher target concentrations than to altered pharmacokinetic disposition in patients with cystic fibrosis. We conclude that the initial dose of gentamicin to achieve a peak of 8 to 12 micrograms/mL and a trough of less than 2.0 micrograms/mL in patients with cystic fibrosis should be 3 mg/kg administered every 6 hours in children and every eight hours in adults. Subsequent dosage adjustment should be made on the basis of a pair of peak and trough serum concentration measurements obtained after the fifth dose. Dosing intervals in this patient population generally should be no shorter than every 6 hours, even if the initial trough concentration is less than 1 microgram/mL.


Assuntos
Fibrose Cística/tratamento farmacológico , Gentamicinas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Fibrose Cística/sangue , Feminino , Gentamicinas/sangue , Humanos , Masculino
10.
Chest ; 88(2 Suppl): 103S-111S, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-3893922

RESUMO

Theophylline has emerged as a major prophylactic agent for controlling the symptoms of chronic asthma, but it provides little if any relief of pulmonary symptoms caused by irreversible chronic airways obstruction. Although in vitro it inhibits phosphodiesterase and antagonizes adenosine receptors, theophylline's mechanism of action in asthma is unknown. Often, 10 to 20 micrograms/ml is used as the range of serum concentrations where there is the greatest likelihood of obtaining maximal benefit safely. Slow-release products have the potential to provide more stable serum concentrations with longer dosing intervals. However, clinically important differences in rate and sometimes extent of absorption exist between the 15 formulations sold under 29 brand names in this country. In patients with more rapid elimination, few products have sufficiently slow absorption to allow twice-daily use. Often these formulations must be administered every eight hours to prevent breakthrough in asthmatic symptoms despite promotional claims to the contrary. In patients with slower elimination, differences among products are unlikely to be clinically important with 12-hour dosing intervals. Current products approved for "once-a-day" dosing are clinically inadequate because of erratic absorption or excessive serum concentration fluctuations. Moreover, food induces dose dumping of potentially toxic amounts of theophylline from Theo-24, greatly increases the extent of absorption of theophylline from Uniphyl, decreases extent of absorption from Theo-dur-Sprinkle capsules, but has no clinically important effect on Theo-Dur tablets, Theobid, Slo-Bid, or Somophyllin-CRT. The effects of food or other factors that alter gastrointestinal physiology on theophylline absorption are unknown for most other products.


Assuntos
Pneumopatias Obstrutivas/tratamento farmacológico , Teofilina/farmacologia , Asma/sangue , Asma/tratamento farmacológico , Biotransformação , Preparações de Ação Retardada , Interações Medicamentosas , Alimentos , Humanos , Absorção Intestinal , Cinética , Fígado/metabolismo , Pneumopatias Obstrutivas/sangue , Pneumopatias Obstrutivas/metabolismo , Taxa de Depuração Metabólica , Teofilina/administração & dosagem , Teofilina/análise , Teofilina/metabolismo
11.
Am J Hosp Pharm ; 41(12): 2642-6, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6393759

RESUMO

A modification of the EMIT-Tox qualitative serum barbiturate assay (Syva Company, Palo Alto, CA) was evaluated for measuring pentobarbital concentrations. Pentobarbital calibrator solutions were substituted for the secobarbital calibrators provided with the assay kit, and control solutions of pentobarbital were used to determine the modified assay's precision and accuracy. Specificity for pentobarbital with respect to other barbiturates and assay interference from other drugs were evaluated in vitro. Serum samples obtained from 49 patients receiving intravenous pentobarbital sodium to treat intracranial hypertension were assayed by gas-liquid chromatography (GLC) and by the modified EMIT procedure. Samples from patients who were receiving both phenobarbital and pentobarbital (9 of 49) were assayed for both drugs, interference curves were plotted, and the corrected pentobarbital concentrations were compared with GLC values. The modified assay method provided an accurate measurement of serum pentobarbital concentrations of 1-30 micrograms/ml. Significant cross-reactivity with the pentobarbital assay was present for secobarbital, butabarbital, allobarbital, and phenobarbital. Dexamethasone, dopamine, phenytoin, cimetidine, lidocaine, diazepam, morphine, and several other drugs at concentrations of 1000 micrograms/ml did not interfere with the assay. There was a strong correlation between the GLC reference method and the modified EMIT assay (r = 0.96). Clinically important cross-reactivity with phenobarbital was found; the corrected pentobarbital concentrations for patients who had received phenobarbital strongly correlated with GLC results (r = 0.98). The modified assay appears to be sufficiently reliable for determination of pentobarbital serum concentrations.


Assuntos
Pentobarbital/sangue , Cromatografia Gasosa/métodos , Reações Cruzadas , Estudos de Avaliação como Assunto , Humanos , Técnicas Imunoenzimáticas , Pressão Intracraniana
12.
Clin Pharmacokinet ; 9(2): 95-135, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6370542

RESUMO

In order to achieve the greatest chance for maximum benefit from theophylline in the management of chronic asthma, the serum concentration should be maintained in the therapeutic range of 10 to 20 micrograms/ml. Conventional rapid release formulations produce excessive fluctuations in serum concentrations that can result in variability in clinical response between doses. In contrast, slow release formulations have the potential to achieve relatively constant serum concentrations with 12-hour dosing intervals, thus providing around-the-clock stabilisation of the hyper-reactive airways that characterise chronic asthma. Furthermore, the decreased frequency of dosing with these formulations can improve patient compliance. However, significant differences in rate and extent of absorption exist between the available formulations. Single-dose bioavailability studies comparing a slow release product with an oral solution or plain uncoated tablet in a crossover design permit examination of the rate and extent of absorption. Comparison of a slow release product with an oral reference following multiple doses at steady-state permits examination of the extent but generally not rate of absorption. The mean fraction absorbed-time profile, calculated from a modification of the Wagner-Nelson equation, is a process-independent method of comparing rates of absorption of different products after single doses. A prospective study in 14 children with chronic asthma has demonstrated that this modified equation, when rearranged to iteratively solve for serum concentrations, can accurately predict steady-state serum concentrations for different dosing intervals in patient populations with different rates of elimination. When slow release products are compared in this manner at 8- or 12-hour dosing intervals for patients with slow elimination, clinically relevant differences between brands are not apparent. However, in patients with rapid elimination, i.e. children, cigarette smokers, and 25% of non-smoking adults, application of this method shows that only some formulations (i.e. 'Slo-Bid Gyrocaps' and 'Theo-Dur', which is also marketed under different brand names names such as 'Sustaire', 'Pulmi-Dur' and 'Theolin Retard') can maintain serum concentrations within the therapeutic range for an entire 12-hour dosing interval. More rapidly absorbed slow release products must be administered at 8-hour dosing intervals in patients with rapid elimination, despite promotional claims to the contrary. Current products promoted for once-a-day administration are clinically inadequate because of incomplete and erratic absorption, and/or excessive serum concentration fluctuations.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Teofilina/metabolismo , Administração Oral , Asma/tratamento farmacológico , Asma Induzida por Exercício/prevenção & controle , Disponibilidade Biológica , Preparações de Ação Retardada , Alimentos , Humanos , Absorção Intestinal , Cinética , Cooperação do Paciente , Teofilina/administração & dosagem
13.
Ther Drug Monit ; 5(3): 359-62, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-6356497

RESUMO

Using the EMIT assay, we tested clinical samples from patients receiving 12 commonly monitored drugs to evaluate the effect of serum separator gel contained in serum separator blood collection tubes (SST) (Becton-Dickinson). There were significant concentration decreases for lidocaine, pentobarbital, and phenytoin. In vitro experiments demonstrated that this effect on phenytoin was dependent on time of exposure to the gel and volume of whole blood, but was not dependent on the presence of red blood cells or initial concentration. Bias attributed to the use of SST could interfere with the usefulness of clinical results at the upper and lower limits of the therapeutic range. This problem can be minimized by processing samples of at least 2 ml within 1 h.


Assuntos
Coleta de Amostras Sanguíneas/instrumentação , Preparações Farmacêuticas/sangue , Tratamento Farmacológico , Géis , Humanos , Técnicas Imunoenzimáticas , Cinética
14.
Eur J Respir Dis Suppl ; 109: 103-19, 1980.
Artigo em Inglês | MEDLINE | ID: mdl-7002576

RESUMO

Recent definition of the pharmacodynamics and pharmacokinetic characteristics of theophylline and readily available, specific assays have increased the therapeutic benefits from this drug while decreasing the risk of toxicity. Once familiarity is achieved with the various factors that alter clearance, such as age, smoking habits, physiological abnormalities, and concurrent drug therapy, initial dosage can be appropriately individualized. Careful product selection, the slow progressive titration of dose over nine days, and the accurate measurement and interpretation of serum theophylline concentration prevent adverse effects and interactions. However, long-term therapy with theophylline should probably be avoided when other alternatives are available in patients with cor pulmonale, liver dysfunction, cardiac decompensation, migraine headaches, and seizure disorders.


Assuntos
Teofilina/efeitos adversos , Interações Medicamentosas , Humanos , Teofilina/sangue , Teofilina/uso terapêutico
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