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.


METHODS
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.


CONCLUSIONS
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.
Konishi
Hiroki
H
Department of Hospital Pharmacy, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan. konishi@belle.shiga-med.ac.jp
Nakatsuka
Takayuki
T
Yoshida
Michiaki
M
Tamaki
Shinji
S
Minouchi
Tokuzo
T
Yamaji
Akira
A
Kinoshita
Masahiko
M
D000328:Adult; D001682:Biological Availability; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007408:Intestinal Absorption; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016312:Treatment Refusal; D014665:Vasodilator Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use
D014665:Vasodilator Agents; D013806:Theophylline