Purine-2(3H),6(1H)-dione

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

other: hospital admission data

Adequacy of study:

supporting study

Reliability:

other: Not applicable

Rationale for reliability incl. deficiencies:

other: Not applicable - hospital admission data

Data source

Reference

Reference Type:

publication (copyright not owned for reproduction)

Title:

Hospital Admission for Xanthine Toxicity

Author:

Derby LE, Jick SS, Langlois JC, Johnson LE, and Jick H

Year:

1990

Bibliographic source:

Pharmacotherapy, 10(2):112-114

Materials and methods

Type of study / information:

Hospitalization admission data

Endpoint addressed:

other: toxicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The incidence rate of hospitalization due to test substance toxicity was reported.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Purine-2(3H),6(1H)-dione

EC Number:

200-718-6

EC Name:

Purine-2(3H),6(1H)-dione

Cas Number:

69-89-6

Molecular formula:

C5H4N4O2

IUPAC Name:

xanthine

Specific details on test material used for the study:

Purity: not reported

Results and discussion

Results:

A follow-up study of 35,909 outpatients who filled more than 220,000 prescriptions for theophylline over 9 years revealed 30 hospitalizations for xanthine toxicity. The overall estimated incidence rate of 7.8/10,000 person-years at risk indicates that in this population, hospitalization for xanthine toxicity is a relatively rare event.

Applicant's summary and conclusion

Executive summary:

Theophylline and other xanthine derivatives have a long history of use for both acute bronchodilation and prophylaxis for pulmonary disorders. While these preparations have been demonstrated to have beneficial effects at therapeutic blood levels, toxicity can occur at levels just above the therapeutic range. The manifestations of theophylline toxicity vary from relatively minor complaints, such as nausea and vomiting, to more serious problems, such as arrhythmias and seizures. Although numerous case reports have described theophylline toxicity, the overall risk of hospitalization for this problem is not known. The authors examined the frequency of hospitalization for toxicity attributable to outpatient use of theophylline at GHC, a health maintenance organization (HMO) in Seattle, Washington, from 1978 to 1987. In the GHC population, 35,909 people filled a total of 223,137 prescriptions for theophylline over the 9 years of study. There were only 30 admissions for theophylline toxicity. Thus, the overall risk for hospitalization for toxicity was estimated to be about 7.8/10,000 person-years at risk, making it a relatively rare event. The low frequency of hospitalization combined with the fact that no deaths were recorded over 9 years suggests that at GHC, theophylline, a xanthine derivative, is a relatively low-risk drug for serious toxicity.