THE EFFECTS OF CHRONIC ACETAMINOPHEN ADMINISTRATION ON THE DISPOSITION OF THE DRUG AND THE BODY STORES OF SULPHATE
Date
1985
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Acetaminophen is a common non-prescription drug used as an analgesic for mild to moderate pain, and as an antipyretic. In therapeutic doses, it is well tolerated but ingestion of excessive amounts of acetaminophen (greater than 5 g) is associated with hepatotoxicity.
The present study examined the effects of long term ingestion of therapeutic dosages of acetaminophen. Little information is known about the effects of acetaminophen on important cosubstrates (sulfate and glutathione, in particular) during chronic administration. Of particular importance are the recent findings that even a single dose of 1.5 g of acetaminophen. can cause partial depletion of body stores of sulfate in man (Morris & Levy, 1983).
To study the effects of acetaminophen on sulfate levels in the body, a turbidimetric assay for the determination of inorganic sulfate in biological fluids was used. Acetaminophen and key metabolites in urine were analyzed by a rapid, sensitive and specific high pressure liquid chromatographic procedure. Calibration curves were linear over the concentration range , of acetaminophen and metabolites expected. Extraction efficiency for acetaminophen from serum was 82.5 (+2.3 SD)%.
The study included nine (9) healthy volunteers and ten (10) patients receiving acetaminophen on a chronic basis. Volunteers participated on two occasions; on the first, each received a single 650 mg oral dose of acetaminophen, and the second time, each received a total of 3.25 g of acetaminophen over a 30 hour time period (650 mg every 6 hours). Patients participating in the study were maintained on their normal treatment and dosage schedules. Concentration of acetaminophen in serum (over 8 h for the volunteer studies; single sample for patients) and acetaminophen and its metabolites in urine (24 hour collection for volunteers; single void for patients) were determined.
The maximum serum concentration of acetaminophen ranged from 3.79 — 8.63 µg/mL for the single dose and 6.81 - 29.63 µg/mL for multiple dosing in volunteers. Mean values for C max were significantly higher in the multiple dose study (13.29 * 6.35 µg/mL) compared to the single dose (7.12 * 1.36 µg/mL) (p< 0.05). However accumulation was not greater than predicted based on the half-life and dosing interval, indicating that the overall disposition of, acetaminophen did not differ significantly after multiple dosing.
Description
Keywords
chronic administration of Acetaminophen, sulfate levels
Citation
Degree
Master of Science (M.Sc.)
Department
Pharmacy