Pharmacokinetic Analysis of Theophylline to Assess Noncompliance in Therapy

OBJECTIVE: To report a case showing patient noncompliance, supported by outcomes of pharmacokinetic analysis of theophylline as a surrogate drug. CASE SUMMARY: A 45-year-old woman with severe hypertension was treated with a variety of oral antihypertensive drugs, but there was no improvement in her elevated blood pressure. Since we suspected that her intestinal drug absorption capacity was impaired, a theophylline absorption test was performed. When oral theophylline was given to the patient in tablet form, the apparent bioavailability was only 20%, which agreed with our hypothesis. However, the bioavailability of theophylline given in liquid form was almost 100%, and theophylline in tablet form was confirmed to be fully bioavailable when the test was performed under supervision by medical staff. DISCUSSION: The almost complete bioavailability of oral theophylline indicated that there was no impairment in intestinal absorption capacity. The low bioavailability of theophylline observed after tablet administration in the first trial was apparently a result of noncompliance, because the staff did not supervise administration to ensure that tablets were swallowed. Thus, the low response to antihypertensive therapy was attributed to patient noncompliance in taking the drugs, despite her insistence to the contrary. CONCLUSIONS: The use of theophylline was a novel approach to evaluating the absorbability of orally administered drugs in a patient suspected of poor compliance with therapy. A great difference in theophylline bioavailability between the supervised and unsupervised trials was strongly indicative of patient noncompliance. The possibility of impaired absorption was virtually ruled out.

Prevention of drug absorption in simulated theophylline overdose

1 The effects of emesis, gastric lavage and oral activated charcoal on theophylline absorption were compared in healthy volunteers. 2 One of four regimes (ipecacuanha-induced emesis, gas tric lavage, oral activated charcoal and no treatment) was randomly chosen one hour after a simulated over dose with sustained-release theophylline on four sepa rate occasions in twelve healthy volunteers. 3 Syrup of ipecacuanha produced emesis in all twelve volunteers but only seven vomited any tablets. Gastric lavage yielded tablets in only one volunteer. 4 The mean systemic availabilities (areas under the con centration-time curves relative to control) of theo phylline for ipecacuanha-induced emesis, gastric lavage and charcoal, were 107.1%, 101.1% and 16.9%, respectively. 5 Oral activated charcoal was thus highly effective, while gastric lavage and emesis were ineffective in pre venting theophylline absorption. Activated charcoal is potentially the most effective first-line treatment for acute overdosage with sustained-release theophylline tablets.