INTRAVITREAL GANCICLOVIR PHARMACOKINETICS IN RABBITS AND MAN

被引：23

作者：

ASHTON, P

BROWN, JD

PEARSON, PA

BLANDFORD, DL

SMITH, TJ

ANAND, R

NIGHTINGALE, SD

SANBORN, GE

机构：

[1] Department of Ophthalmology, Kentucky Clinic, University of Kentucky, Lexington, Kentucky

[2] New England Glaucoma Research Foundation, Boston, Massachusetts

[3] Southwestern Medical Center, Dallas, Texas

[4] Richmond Retina Associates, Richmond, Virginia

来源：

JOURNAL OF OCULAR PHARMACOLOGY | 1992年 / 8卷 / 04期

关键词：

D O I：

10.1089/jop.1992.8.343

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

引用

页码：343 / 347

页数：5

共 14 条

[1]

Jabs D.A., Enger C., Bartlett J.G., Cytomegalovirus retinitis and acquired immunodeficiency syndrome, Arch. Ophthalmol, 107, pp. 75-80, (1989)

[2]

Mortality in patients with acquired immunodeficiency syndrome treated with either foscarnet or ganciclovir, New Eng. J. Med, 4, pp. 213-220, (1992)

[3]

Henry K., Cantrill H., Fletcher C., Chinnock B.J., Balfour H.H., Use of intravitreal ganciclovir (dihydroxy propoxymethyl guanine) for cytomegalovirus retinitis in a patient with AIDS, Am. J. Ophthalmol, 103, pp. 17-23, (1987)

[4]

Jabs D.A., Newman C., De Bustros S., Polk B.F., Treatment of cytomegalovirus retinitis with ganccclovir, Ophthalmology, 94, pp. 824-830, (1987)

[5]

Smith T.J., Pearson A.P., Blandford D.L., Brown J.D., Goins K.A., Hollins J.A., Schmeesser E.T., Glavinos P., Baldwin L.B., Ashton P., Intravitreal sustained release ganciclovir, Arch. Ophthalmol, 110, pp. 255-258, (1992)

[6]

Sanborn G.E., Anand R., Torti R., Nightingale S.D., Cal S.X., Yates B., Ashton P., Smith T.J., Sustained release ganciclovir therapy for CMV retinitis using an intravitreal device, Arch. Ophthalmol, 110, pp. 188-195, (1992)

[7]

Gloor B.P., The vitreous, Alder's Physiology of the Eve Clinical Applications, pp. 246-267, (1987)

[8]

Warwick R., The Eyeball, Eugene Wolff's Anatomy of the Eve and Orbit, pp. 30-180, (1976)

[9]

Prince J.H., In The Rabbit in Eye Research, (1964)

[10]

Prince J.H., In The Rabbit in Eye Research, (1964)

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