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Intraocular pressure-lowering effect of oral paracetamol and its in vitro corneal penetration properties

Authors Mohamed N, Meyer D

Received 24 September 2012

Accepted for publication 14 November 2012

Published 30 January 2013 Volume 2013:7 Pages 219—227


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Nabiel Mohamed, David Meyer

Division of Ophthalmology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa

Background: Several studies have confirmed the ability of cannabinoids to reduce intraocular pressure. Experimental data recently demonstrated unequivocally that the analgesic effect of paracetamol is due to its indirect action on cannabinoid receptors. The question then arises as to whether paracetamol can reduce intraocular pressure via its effect on intraocular cannabinoid receptors.
Methods: A 2-week, prospective, randomized, controlled, single-center, parallel-group pilot study was carried out to determine the efficacy and safety of paracetamol 1 g orally administered every 6 hours in adult patients with primary or secondary open angle glaucoma as compared with topical levobunolol 0.5% twice a day. Patient well-being was closely monitored throughout the study and focused on hepatic safety in accordance with Drug-Induced Liver Injury Network criteria. The in vitro diffusion kinetics of acetaminophen in a phosphate-buffered solution in rabbit and human corneas was also investigated, with the view to a topical application.
Results: Eighteen adult patients were enrolled in the study, with nine in the topical levobunolol group and nine in the oral paracetamol group. In the levobunolol group, the mean reduction in intraocular pressure at day 7 was 7.5 mmHg (P < 0.008) and at day 14 was 9.1 mmHg (P < 0.005), from a mean baseline intraocular pressure of 29.6 mmHg. The corresponding figures for the paracetamol group were 8.8 mmHg (P < 0.0004) at day 7 and 6.5 mmHg (P < 0.004) at day 14, from a mean baseline intraocular pressure of 29.4 mmHg. Both study regimens were well tolerated. No serious treatment-related adverse events were reported in either of the treatment groups. Liver function tests, systolic/diastolic blood pressure, or heart rate remained unchanged in both groups during the 2 weeks of the study. In the laboratory study, paracetamol 1 mg/mL in phosphate-buffered solution (pH 7.4) showed acceptable flux rates. Steady-state levels were achieved within 12 hours, thus confirming that paracetamol penetrates the cornea well.
Conclusion: Paracetamol 1 g taken orally every 6 hours reduced open angle glaucoma and/or angle recession glaucoma in both groups of patients, in a way comparable with that achieved by a topical beta-adrenergic receptor antagonist.

Keywords: acetaminophen, paracetamol, glaucoma, intraocular pressure, cannabinoids

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