Oral theophylline dosage for the management of chronic asthma

Theophylline dosage requirements to maintain serum concentrations of 10 to 20 microgram/ml among asthmatic patients were examined in 156 children, ages 2 1/2 months to 16 years, and 33 otherwise health adults. Using 100% bioavailable preparations, low doses were used initially and increased, if tolerated, at three-day intervals. Final dosage was based on serum theophylline measurements which were subsequently repeated after six or more months of therapy. Dosage standardized by weight averaged 24.1 +/- 5.5 mg/kg/day (mean +/- SD) among the 77 children under age 9 years. Age-related variability of weight-adjusted doses were not observed for younger children, but average dose requirements decreased progressively beyound age 9 years to 13 mg/kg/day for patients beyoung 16 years of age. Although interpatient variability in dosage was confirmed at all ages, intrapatient variability in requirements over an average eight-month interval were small; dosage changes to maintain therapeutic serum concentration were primarily associated with growth. These data allow age-specific guidelines for dosage recommendations based on the likelihood of optimally effective and potentially toxic serum theophylline concentrations.     

Theophylline for treatment of asthma.

Theophylline has become useful not just as an acute bronchodilator, but also as a major prophylactic agent for the suppression of symptoms of chronic asthma. Efficacy and toxicity both relate closely to serum concentration. Variable elimination rates for the drug among individuals require careful individualization of dosage guided by measurement of serum theophylline concentration to maintain safe and effective serum theophylline concentrations. Fixed-dose combinations with ephedrine are more likely to add toxicity than benefit compared with theophylline alone if the latter is used in an adequate dose. Choices among the vase array of products available can be further simplified by considering cost and convenience of the various formulations. When used appropriately, theophylline has been successful in the essential elimination of asthmatic symptoms in over 70% of asthmatic children seen at a tertiary care referral center.     

Antithyroid drug therapy for toxic diffuse goiter (Graves disease): thirty years experience in children and adolescents.

Since 1946 104 children and adolescents with toxic diffuse goiter have been treated. Sixty-seven were treated with a thioamide for more than 12 months. Remission occurred in 61%. Twenty-five patients had a 12-hour perchlorate discharge test to determine the least frequent dose schedule required for disease control: 68% could be controlled on a single daily dose and an additional 25% on an every 12-hour schedule. A one-hour radioiodine uptake on combined therapy and change in thyroid gland size during treatment were found to be highly correlated with the presence of a spontaneous remission. Thirty-six patients have been treated by subtotal thyroidectomy. To date 65% have developed permanent hypothyroidism. In the author's opinion, thoamides are the treatment of choice for the majority of children and adolescents.     

Therapeutic problems arising from the use of the intravenous route for drug administration.

The kinetics of drug delivery were studied under conditions of varying iv flow rates and varying sites of drug administration into an iv system. The iv sites and rates were selected on the basis of questionnaire data obtained from nursing personnel. The rate of drug delivery from the iv system was dependent upon the iv flow rate and site of injection of the drug into the iv system. Under conditions of slow iv flow rates (3 ml/hour) there was the expected time delay required for the drug to begin to be infused but an unanticipated protracted time required for actual completion of the drug infusion. Calculation of theoretical drug blood levels based on the results of these iv studies revealed very different blood levels of drug at respective times, including different peak concentrations, depending on the iv flow rate and site at which the drug was injected into the system. Failure to appreciate the effects of slow iv rates and distal iv injection sites on actual rates of drug administration can adversely affect pharmacokinetic decisions and conceivably influence therapeutic success or failure.