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Use of a pharmacokinetic method for establishing doses of aminophylline to treat acute bronchospasm.

Salvador Pancorbo, Scott Davies, Joanne L. Raymond

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Abstract

A pharmacokinetic method of establishing individualized doses of aminophylline in patients with acute bronchospasm was evaluated. Patients admitted to a hospital who required intravenous aminophylline for bronchodilation were studied. Blood samples were drawn before treatment for theophylline-content measurement. Loading doses were administered intravenously and half-lives and volumes of distribution were determined. Individualized constant-rate infusions based on pharmacokinetic data were then begun. Heart rate, nausea, vomiting, seizures, and serum theophylline content were monitored during the study. The mean age of the 55 patients in the study was 54.3 years (range: 7 to 87). Patients with congestive heart failure or liver disease numbered 32; 30 patients were smokers. At approximately 24 hours after the calculated constant-rate infusion was begun, 85% of the patients had therapeutic serum levels of theophylline; 11% of the patients had subtherapeutic levels and 4% had toxic levels. All measured concentrations were between 7.5 and 23.0 microgram/ml. The study method produced significantly more patients in the therapeutic range than would have occurred if previously reported standardized methods had been used (p less than 0.05). Most patients had a decreased heart rate after treatment. No other adverse effects occurred that were attributable to i.v. aminophylline. It is concluded that, for patients in acute bronchospasm, individualizing i.v. aminophylline doses with patient-specific pharmacokinetic data can increase significantly the number of patients who rapidly attain therapeutic serum theophylline levels.

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What this paper is about

A pharmacokinetic method of establishing individualized doses of aminophylline in patients with acute bronchospasm was evaluated. Patients admitted to a hospital who required intravenous aminophylline for bronchodilation were studied. Blood samples were drawn before treatment for theophylline-content measurement. Loading doses were administered intravenously and half-lives and volumes of distribution were determined. Individualized constant-rate infusions based on pharmacokinetic data were then begun. Heart rate, nausea, vomiting, seizures, and serum theophylline content were monitored during the study. The mean age of the 55 patients in the study was 54.3 years (range: 7 to 87). Patients with congestive heart failure or liver disease numbered 32; 30 patients were smokers. At approximately 24 hours after the calculated constant-rate infusion was begun, 85% of the patients had therapeutic serum levels of theophylline; 11% of the patients had subtherapeutic levels and 4% had toxic levels. All measured concentrations were between 7.5 and 23.0 microgram/ml. The study method produced significantly more patients in the therapeutic range than would have occurred if previously reported standardized methods had been used (p less than 0.05). Most patients had a decreased heart rate after treatment. No other adverse effects occurred that were attributable to i.v. aminophylline. It is concluded that, for patients in acute bronchospasm, individualizing i.v. aminophylline doses with patient-specific pharmacokinetic data can increase significantly the number of patients who rapidly attain therapeutic serum theophylline levels.

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Available abstract

A pharmacokinetic method of establishing individualized doses of aminophylline in patients with acute bronchospasm was evaluated. Patients admitted to a hospital who required intravenous aminophylline for bronchodilation were studied. Blood samples were drawn before treatment for theophylline-content measurement. Loading doses were administered intravenously and half-lives and volumes of distribution were determined. Individualized constant-rate infusions based on pharmacokinetic data were then begun. Heart rate, nausea, vomiting, seizures, and serum theophylline content were monitored during the study. The mean age of the 55 patients in the study was 54.3 years (range: 7 to 87). Patients with congestive heart failure or liver disease numbered 32; 30 patients were smokers. At approximately 24 hours after the calculated constant-rate infusion was begun, 85% of the patients had therapeutic serum levels of theophylline; 11% of the patients had subtherapeutic levels and 4% had toxic levels. All measured concentrations were between 7.5 and 23.0 microgram/ml. The study method produced significantly more patients in the therapeutic range than would have occurred if previously reported standardized methods had been used (p less than 0.05). Most patients had a decreased heart rate after treatment. No other adverse effects occurred that were attributable to i.v. aminophylline. It is concluded that, for patients in acute bronchospasm, individualizing i.v. aminophylline doses with patient-specific pharmacokinetic data can increase significantly the number of patients who rapidly attain therapeutic serum theophylline levels.

Key concepts: Aminophylline, Bronchospasm, Theophylline, Medicine, Pharmacokinetics, Anesthesia, Vomiting, Therapeutic index

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