ABSTRACT
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.
Subject(s)
Acute Kidney Injury/metabolism , Theophylline/pharmacokinetics , Acute Kidney Injury/therapy , Asthma/drug therapy , Child, Preschool , Humans , Male , Metabolic Clearance Rate , Peritoneal Dialysis , Theophylline/adverse effects , Theophylline/metabolism , Uric Acid/analogs & derivatives , Uric Acid/bloodABSTRACT
A method has been developed for the simultaneous determination of methylxanthines and many of their metabolites in plasma. Specially developed extraction columns (Celute-MX) were used and the extracts were separated on a 25-cm ODS column (particle size, 3 microns) at 50 degrees C with a mobile phase gradient. The compounds were detected with a diode array detector at two analytical wavelengths. The value of drug metabolite ratios has been explored and elevated ratios have been found when metabolic clearance was impaired by disease or co-administered drugs. Large concentrations of pharmacologically active metabolites have been found in renal failure. The assay has proved to be reliable and valuable in the elucidation of therapeutic and metabolic problems involving the methylxanthines.
Subject(s)
Caffeine/blood , Chromatography, High Pressure Liquid/methods , Theophylline/blood , Caffeine/metabolism , Humans , Theophylline/metabolism , Xanthines/blood , Xanthines/metabolismABSTRACT
Blood was collected from 77 patients for estimation of theophylline concentration by whole blood assay using an immunochromatographic stick (Acculevel, Syva UK, Maidenhead, Berkshire). Results were validated by high performance liquid chromatography (HPLC). The stick method was rapid, reliable, required no technical expertise, and produced results equivalent to those obtained from assay from HPLC.
Subject(s)
Theophylline/blood , Adolescent , Asthma/blood , Child , Child, Preschool , Chromatography, High Pressure Liquid , Humans , Immunoenzyme Techniques , Infant , MethodsABSTRACT
A 58-year-old man with a history of alcoholic liver disease and chronic airflow obstruction presented with heart failure and acute bronchitis. 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. After 3 weeks on a caffeine-free diet theophylline and caffeine challenge tests were performed which demonstrated the ease with which caffeine could accumulate. The importance of caffeine accumulation during theophylline therapy is discussed.
