Differences in ocular surface irritation between timolol hemihydrate and timolol maleate.
OBJECTIVE
We evaluated the anterior segment surface reaction findings between timolol hemihydrate and timolol maleate. The only known difference between these preparations is the maleate salt.


METHODS
After a baseline examination, we randomized 28 healthy subjects (26 completed) to timolol hemihydrate or timolol maleate given in both eyes twice daily, in a double masked fashion, for 1 week. Subjects then were evaluated at the morning trough (hour 0 examination), dosed, and re-evaluated in 1 hour (hour 1 examination). Subjects were left untreated for 1 week and then switched to the opposite medication for the second study period.


RESULTS
Corneal staining (graded 0 to 4) for timolol maleate was worse between baseline (0.9) and hour 0 (1.4; P =.009) and baseline and hour 1 (1.4; P =.011). Also, mean punctate corneal staining for timolol maleate was increased from baseline (22.6) to hour 0 (31.7; P =.033) and showed borderline significance to hour 1 (33.4; P =.058), and for timolol hemihydrate there was a borderline significant elevation from baseline (24.2) to hour 1 (29.8; P =.060). When treatment groups were compared, there was a greater change in corneal staining with timolol maleate than timolol hemihydrate from baseline to hour 0 (P =.020) and greater staining with timolol maleate than timolol hemihydrate at hour 0 (P =.032). Nasal conjunctiva showed increased mean staining with timolol maleate from baseline (23.6, P =.035) to hour 0 (29.5, P =.035) and to hour 1 (31.9 P =.038) but not with timolol hemihydrate. There were increased symptoms of ocular dryness from baseline to hour 0 with timolol maleate (P =.012) but not with timolol hemihydrate.


CONCLUSIONS
The study suggests that timolol maleate potentially may have more of an irritant effect than timolol hemihydrate on the corneal and nasal conjunctival epithelium.
Stewart
W C
WC
Pharmaceutical Research Corporation, Charleston, South Carolina 29412-2464, USA.
Stewart
J A
JA
Holmes
K T
KT
Leech
J N
JN
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D004311:Double-Blind Method; D004341:Drug Evaluation; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D007509:Irritants / Q000494:pharmacology; D008297:Male; D009883:Ophthalmic Solutions; D012449:Safety; D013999:Timolol / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D007509:Irritants; D009883:Ophthalmic Solutions; D013999:Timolol