Skin irritation induced by topically applied timolol.
1. Erythema induced by topically applied timolol, a non-selective beta-adrenoceptor blocker, was assessed in six male volunteers. Intensity of erythema developed on the inner surface of the left forearm where timolol free base was applied for 10 h was measured by a visual score, laser doppler flowmeter and reflectance spectrophotometry. Plasma timolol concentrations collected from the left and right arms were also measured. 2. The mean values for blood volume and blood flow per unit volume of tissue both of which were assessed by a laser doppler flowmeter, haemoglobin index measured by reflectance spectrophotometry, and magnitude of erythema graded by a visual score significantly increased after the application of an acrylic co-polymer adhesive patch containing 20% (w/v) timolol free base. 3. Plasma timolol concentrations collected from the left antecubital vein were 2.4 to 10.7 times greater than those from the right arm and had significant correlations (rs = 0.55 to 0.76) with the parameters indicating the extent of erythema developed where a patch containing timolol was applied. 4. The inter-individual variation of timolol was attributed to that of the diffusivity of timolol through skin rather than that of the skin reactivity to topically applied timolol because the plasma timolol concentrations drawn from the left arm in the subjects who did not develop erythema were very low.(ABSTRACT TRUNCATED AT 250 WORDS)
Kubota
K
K
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Koyama
E
E
Yasuda
K
K
D000287:Administration, Topical; D000328:Adult; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D007509:Irritants; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000098:blood supply / Q000187:drug effects*; D013999:Timolol / Q000009:adverse effects* / Q000097:blood
D007509:Irritants; D013999:Timolol