జర్నల్ ఆఫ్ క్లినికల్ & ఎక్స్‌పెరిమెంటల్ ఫార్మకాలజీ

నైరూప్య

Low Doses of Acetaminophen Prolonged Prothrombin Time and Increased International Normalized Ratio in Patients Receiving Long-Term Therapy

Sazan Dakheel*

Abstract Objectives: Acetaminophen is one of the safest and effective antipyretic and analgesic medications. Long term administration of this medication appeared to interfere with the activity of two key enzymes of the vitamin K cycle. The primary end point of this study was to evaluate the chronic effect of acetaminophen on Prothrombin Time (PT) and International Normalized Ratio (INR) parameters. Methods: Prospective, longitudinal , double-blind, placebo-controlled study was performed in Kurdistan region of Iraq, patients suffering from mild headache were prepared to take acetaminophen 500 mg twice daily for at least (8) months. PT, INR, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured for both patient and control groups before drug administration and then every month. Results: The main consequence of the study was the difference in mean PT and INR between control group and group receiving acetaminophen long term therapy for 8 months. In patients on acetaminophen (1 g/day), the mean observed PT and INR were significantly elevated during therapy period. The significant differences in mean PT started from the second month of therapy (12.910 ± 0.098) in patients on acetaminophen versus (12.083 ± 0.077) in control participants (P<0.01). The maximum variations of mean PT was observed after eight months in patients on acetaminophen compared with the control participants (18.903 ± 0.184 vs. 12.300 ± 0.066, P< 0.01). Likewise the mean observed INR was significantly increased after the second month of treatment (1.123 ± 0.013) in patients on acetaminophen versus (1.006 ± 0.101) in control subjects (P<0.01). As well, maximum variations of mean INR observed after eight months in patients on acetaminophen compared with the control participants (2.084 ± 0.033 vs. 1.036 ± 0.008, P<0.01). There was a significant difference of mean ALT observed during the latest three months of study period in patients on acetaminophen compared with the control participants (P<0.01). However a significant value of both PT and INR in all patients rose markedly during the eight months of acetaminophen therapy. Conclusion: The clinical findings of this study support that chronic administration of acetaminophen at low dose (Ig/day) induce a highly significant elevation of PT and INR parameters in all patients participated in this study.