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The Absolute Bioavailability of Oral Theophylline in Patients with Spinal Cord Injury
Author(s) -
Segal Jack L.,
Brunnemann Sherry R.,
Gordon Stanley K.,
Eltorai Ibrahim M.
Publication year - 1986
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1986.tb03446.x
Subject(s) - theophylline , bioavailability , medicine , anesthesia , pharmacokinetics , oral administration , spinal cord injury , spinal cord , pharmacology , psychiatry
The absolute bioavailability of oral theophylline in five tetraplegic, five paraplegic and three control (intact neuraxes) subjects was studied. All were healthy nonobese males between 20 and 60 years of age, with normal renal and hepatic function. More than 1 year had elapsed from the date of injury in all of the patients with spinal cord injury. None of the study subjects was taking medications known to interfere with theophylline metabolism or the analytic methodology. Each received theophylline in an equivalent amount orally, and by intravenous infusion on 2 occasions separated by not less than 2 weeks. The time course of serum theophylline concentration was followed for up to 24 hours and the area under each oral and intravenous curve extrapolated to infinity (AUC O→∞ ) was compared using a linear, least‐squares, best‐fit BASIC program (ESTRIP). A statistically significant difference between means and variances of the absolute bioavailability of oral theophylline, AUC Oral O→∞ /AUC IV O→∞ , (AUC ratio ± SD) was demonstrated in the tetraplegic subjects who showed decreased bioavailability (AUC ratio = 0.67 ± 0.04, range 0.63–0.73) as compared to the paraplegic (AUC ratio = 0.95 ± 0.09, range 0.84–1.08) and control subjects (AUC ratio = 0.90 ± 0.12, range 0.78–1.02). A decrease in the bioavailability of oral theophylline in tetraplegic subjects has not previously been described and may be caused by impaired gastric emptying, which frequently characterizes high myelopathy. Diminished bioavailability could result in underestimation of loading and maintenance doses in tetraplegic humans.