Abstract
1. Outpatients with primary open angle glaucoma uncontrolled on single topical therapy with either pilocarpine or timolol were recruited for a stratified double dummy cross over trial. Once or twice daily sustained release acetazolamide (SRA) was compared with an identical regimen of conventional tablets (CA). 2. During the run in period the patients received 500 mg SRA once or twice daily as needed to control intraocular pressure (IOP). The dose was thereafter kept constant and patients were allocated randomly to 4 weeks treatment with CA followed by 4 weeks SRA or vice versa. IOP and venous plasma concentrations of acetazolamide were measured at weekly intervals. At the end of each 4 week course, patients were admitted for a 24 h profile of IOP and drug concentration measurements. 3. Thirty-five patients were recruited, but eleven were withdrawn during the run in period largely because of adverse effects; these became less troublesome when it was decided to give the once daily dose at 22.00 h. Four were withdrawn during the cross over, two because of inadequate IOP control. Twenty completed the trial. 4. The morning plasma concentration of acetazolamide measured each week showed no tendency to accumulation during the study. The mean swing (maximum minus minimum) in plasma acetazolamide concentration during the 24 h profile was less (P less than 0.005) with the SR formulation (11.6 +/- 4.9; mg l-1) +/- s.d.) than with the conventional (15.5 +/- 4.7) but the mean concentrations over the 24 h profile were indistinguishable (P greater than 0.05; 9.7 +/- 3.8 and 8.6 +/- 2.8 respectively). 5. Satisfactory control of IOP (no more than one reading above 22 mmHg) was maintained despite the changes in formulation in all but two of the patients who entered the cross over study. No close relationship between IOP and plasma concentration of acetazolamide was found. The 24 h IOP profiles whilst receiving each of the formulations were indistinguishable; thus the smoothing of the plasma drug concentration profile achieved by the SR formulation did not reduce the amplitude of swings in IOP. Similarly, no difference was observed between the formulations with respect to adverse effects. 6. It is concluded that the SR and conventional formulations were equivalent with respect to mean plasma acetazolamide concentration, IOP control and adverse effects. The SR formulation did not show practical advantages over the conventional formulation which was equally effective even with dosage intervals of 12 or 24 h.
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Selected References
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- BECKER B. Decrease in intraocular pressure in man by a carbonic anhydrase inhibitor, diamox; a preliminary report. Am J Ophthalmol. 1954 Jan;37(1):13–15. doi: 10.1016/0002-9394(54)92027-9. [DOI] [PubMed] [Google Scholar]
- BECKER B., MIDDLETON W. H. Long-term acetazoleamide (diamox) administration in therapy of glaucomas. AMA Arch Ophthalmol. 1955 Aug;54(2):187–192. doi: 10.1001/archopht.1955.00930020191004. [DOI] [PubMed] [Google Scholar]
- Berson F. G., Epstein D. L., Grant W. M., Hutchinson B. T., Dobbs P. C. Acetazolamide dosage forms in the treatment of glaucoma. Arch Ophthalmol. 1980 Jun;98(6):1051–1054. doi: 10.1001/archopht.1980.01020031041005. [DOI] [PubMed] [Google Scholar]
- Chambers D. M., White M. H., Kostenbauder H. B. Efficient extraction and reversed-phase high-performance liquid chromatography-ultraviolet quantitation of acetazolamide in serum. J Chromatogr. 1981 Sep 11;225(1):231–235. doi: 10.1016/s0378-4347(00)80266-2. [DOI] [PubMed] [Google Scholar]
- DE CARVALHO C. A., LAWRENCE C., STONE H. H. Acetazolamide (diamox) therapy in chronic glaucoma; a three-year follow-up study. AMA Arch Ophthalmol. 1958 Jun;59(6):840–849. doi: 10.1001/archopht.1958.00940070054005. [DOI] [PubMed] [Google Scholar]
- Henkind P., Leitman M., Weitzman E. The diurnal curve in man: new observations. Invest Ophthalmol. 1973 Sep;12(9):705–707. [PubMed] [Google Scholar]
- Kelly R. G. Bioavailability of sustained release acetazolamide. J Pharm Pharmacol. 1986 Nov;38(11):863–864. doi: 10.1111/j.2042-7158.1986.tb04515.x. [DOI] [PubMed] [Google Scholar]
- MOSES R. A. The Goldmann applanation tonometer. Am J Ophthalmol. 1958 Dec;46(6):865–869. doi: 10.1016/0002-9394(58)90998-x. [DOI] [PubMed] [Google Scholar]
- Wistrand P. J. The use of carbonic anhydrase inhibitors in ophthalmology and clinical medicine. Ann N Y Acad Sci. 1984;429:609–619. doi: 10.1111/j.1749-6632.1984.tb12398.x. [DOI] [PubMed] [Google Scholar]