OCULAR DRUG-INTERACTIONS INVOLVING TOPICALLY APPLIED TIMOLOL IN THE PIGMENTED RABBIT

被引:8
作者
LUO, AM [1 ]
SASAKI, H [1 ]
LEE, VHL [1 ]
机构
[1] UNIV SO CALIF,SCH PHARM,DEPT PHARMACEUT SCI,1985 ZONAL AVE,LOS ANGELES,CA 90033
关键词
D O I
10.3109/02713689109003445
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
The objective of this study was to determine whether the ocular and systemic absorption of topically applied timolol in the pigmented rabbit was significantly affected by the coadministration with other eye medications, including pilocarpine, epinephrine, their prodrugs, phenylephrine, tetracaine, and proparacaine. Twenty-five microliters of 0.65% timolol maleate solutions, both in the presence and absence of a second drug, were instilled to the pigmented rabbit eye. Timolol concentrations in anterior segment tissues were monitored at 30 and 90 min, and the time course of timolol concentration in plasma was monitored over 120 min. All coadministered drugs except proparacaine, reduced intraocular timolol concentrations by varying extents depending on the sampling time, while increasing the timolol concentrations in the conjunctiva and sclera. In addition, all coadministered drugs, except pilocarpine, tetracaine, and proparacaine, reduced the systemic absorption of timolol by an average of about 50%. A plausible explanation for the simultaneous reduction in ocular and systemic timolol absorption is changes in tear turnover rate, protein secretion, and binding of timolol to tear proteins, rather than changes in corneal and perhaps conjunctival and nasal permeability, elicited by the second drug. Vasoconstriction on the conjunctival and nasal mucosae is an additional factor possibly contributing to the reduction in systemic timolol absorption by epinephrine, its prodrug, phenylephrine, and perhaps the pilocarpine prodrug. The clinical implication of the above findings is that before instituting combination or multiple drug therapy the possibility of changes in ocular and systemic absorption of the first drug by the second drug must be considered.
引用
收藏
页码:231 / 240
页数:10
相关论文
共 21 条
[1]  
ABERG G, 1978, ACTA OPHTHALMOL, V57, P225
[2]  
BOISSIER JR, 1976, J PHARMACOL-PARIS, V7, P241
[3]   INHIBITION OF EPINEPHRINE OXIDATION IN WEAK ALKALINE-SOLUTIONS [J].
BONEVSKI, R ;
MOMIROVICCULJAT, J ;
BALINT, L .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1978, 67 (10) :1474-1476
[4]   SYMPATHOMIMETIC PROTEIN SECRETION BY YOUNG AND AGED LACRIMAL GLAND [J].
BROMBERG, BB ;
CRIPPS, MM ;
WELCH, MH .
CURRENT EYE RESEARCH, 1986, 5 (03) :217-223
[5]   PILOCARPINE PRODRUGS .2. SYNTHESIS, STABILITY, BIOCONVERSION, AND PHYSICOCHEMICAL PROPERTIES OF SEQUENTIALLY LABILE PILOCARPINE ACID DIESTERS [J].
BUNDGAARD, H ;
FALCH, E ;
LARSEN, C ;
MOSHER, GL ;
MIKKELSON, TJ .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1986, 75 (08) :775-783
[6]  
CHANG SC, 1988, INVEST OPHTH VIS SCI, V29, P626
[7]  
de HAAS E, 1960, Arch Ophthalmol, V64, P34
[8]  
GIBALDI M, 1982, PHARMACOKINETICS, P1
[9]  
HERMAN G, 1978, BIOL CELLULAIRE, V31, P255
[10]  
Knupp J A, 1983, Surv Ophthalmol, V28 Suppl, P280, DOI 10.1016/0039-6257(83)90150-9