Pharmacokinetics of Theophylline and its Metabolites During Acute Renal Failure

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.

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“…Cigarettes, inhalers, and tea were associated with higher spiral scores in our regression model. Nicotine, in cigarettes, is well known to exacerbate tremor,3, 29 as are caffeine30 and methylxanthines,31 in tea. Similarly, asthma inhalers are well known to exacerbate tremor 32.…”

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“…The successful experience of Peyriere et al [2] was therefore unique and worth further study. However, we would caution the use of aminophylline under such circumstances especially in the presence of renal impairment [4].…”