title: Intraocular pressure-lowering effect of oral paracetamol and its in vitro corneal penetration properties.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Ophthalmology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa.
authors: Nabiel
authors: N
authors: Mohamed
authors: David
authors: D
authors: Meyer
keywords: acetaminophen; cannabinoids; glaucoma; intraocular pressure; paracetamol
references: Arch Soc Esp Oftalmol. 2011 Jan;86(1):16-23
references: 21414525
references: Trends Pharmacol Sci. 2000 Feb;21(2):38-40
references: 10733432
references: Ophthalmic Res. 2001 Jul-Aug;33(4):217-20
references: 11464074
references: Pharmacol Rev. 2006 Sep;58(3):389-462
references: 16968947
references: Br J Pharmacol. 2006 Apr;147(8):917-25
references: 16474412
references: CNS Drug Rev. 2006 Fall-Winter;12(3-4):250-75
references: 17227290
references: Cornea. 2001 Jul;20(5):505-8
references: 11413407
references: J Ocul Pharmacol Ther. 2004 Oct;20(5):421-9
references: 15650517
references: Ophthalmic Res. 2007;39(2):69-75
references: 17284931
references: Invest Ophthalmol. 1974 Jun;13(6):422-9
references: 4831696
references: J Biol Chem. 2005 Sep 9;280(36):31405-12
references: 15987694
references: Pharmacol Rev. 1986 Mar;38(1):45-74
references: 2872689
references: N Engl J Med. 1991 Jul 11;325(2):87-91
references: 2052056
references: Brain Res Mol Brain Res. 1998 Jul 15;58(1-2):240-5
references: 9685662
references: JAMA. 2006 Jul 5;296(1):87-93
references: 16820551
references: Exp Eye Res. 1973 Apr;15(4):499-507
references: 4702382
references: J Ocul Pharmacol Ther. 2007 Apr;23(2):146-51
references: 17444803
references: Br J Ophthalmol. 1996 May;80(5):389-93
references: 8695555
references: Eur J Pharmacol. 2006 Feb 15;531(1-3):280-1
references: 16438952
references: Clin Ther. 2006 Feb;28(2):222-35
references: 16678643
references: Mini Rev Med Chem. 2005 Jul;5(7):631-40
references: 16026309
references: Invest Ophthalmol Vis Sci. 2003 Jun;44(6):2565-72
references: 12766058
references: J Med Chem. 1997 Aug 29;40(18):2793-809
references: 9288160
references: Surv Ophthalmol. 1994 Sep-Oct;39(2):123-32
references: 7801220
references: J Ocul Pharmacol Ther. 2002 Oct;18(5):419-27
references: 12419093
references: J Glaucoma. 2006 Oct;15(5):349-53
references: 16988594
references: Trends Mol Med. 2002 Feb;8(2):58-61
references: 11815270
references: Ann Intern Med. 2002 Dec 17;137(12):947-54
references: 12484709
references: Aliment Pharmacol Ther. 2007 Jul 15;26(2):283-90
references: 17593074
references: BMJ. 2002 Sep 28;325(7366):678
references: 12351357
references: Br J Ophthalmol. 2004 May;88(5):708-13
references: 15090428
references: Arch Ophthalmol. 2002 Oct;120(10):1268-79
references: 12365904
references: Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2442-8
references: 10476817
references: Pharm Res. 2001 Apr;18(4):494-9
references: 11451037