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After unsuccessful therapy with salbutamol syrup and inhaled terbutaline a 3-year-old boy with an acute exacerbation of asthma was treated with nebulised salbutamol (albuterol), intravenous aminophylline and hydrocortisone. His condition continued to deteriorate and he required artificial ventilation. Subsequently, he became anuric, with liver dysfunction, nonspecific encephalopathy and limb tremor. Peritoneal dialysis was started. Plasma theophylline concentrations were monitored and maintained in the therapeutic or subtherapeutic range. Despite this, he was hyper-reflexic with limb tremor. Excessively high plasma concentrations of the principal theophylline metabolite, 1,3-dimethyluric acid, were found [maximum 92 mg/L (470 mumol/L)], which cleared only with the return of normal renal function. Plasma concentration monitoring of drugs other than theophylline was not performed. After the patient recovered, a pharmacokinetic study demonstrated that normal methylxanthine metabolism was re-established. Pharmacokinetic analysis indicated that the undue accumulation of the metabolites was a result of an inability to clear these compounds. Thus, pharmacologically and toxicologically active metabolites of theophylline may accumulate in anuric patients on peritoneal dialysis, producing clinical symptoms of toxicity. However, in the present case the possible role of metabolites of other drugs cannot be definitely excluded.

The therapeutic effects of either morning or evening administration of a once-daily controlled release theophylline preparation (Uniphyllin) were studied in 17 asthmatic children. Neither morning nor evening administration produced therapeutic plasma theophylline levels throughout 24h. Similarly, bronchodilation was not maintained during the same period. However, morning peak expiratory flow rates were significantly improved following evening dosage, suggesting a role for evening administration when nocturnal symptoms predominate.

1 A 58-year-old man with a history of alcoholic liver disease and chronic airflow obstruction presented with heart failure and acute bronchitis. 2 Plasma methylxanthines were estimated as a guide to further theophylline therapy and serious caffeine accumulation was noted in the presence of a subtherapeutic concentration of theophylline. 3 After 3 weeks on a caffeine-free diet theophylline and caffeine challenge tests were performed which demonstrated the ease with which caffeine could accumulate. 4 The importance of caffeine accumulation during theophylline therapy is discussed.

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