Bisoprolol--comparative toxicokinetic study after oral and conjunctival administration in beagles.
Beagles were treated with bisoprolol, a beta 1-selective adrenoceptor antagonist, for 30 days with the following daily doses: oral: 30 mg/kg; conjunctival: 0.5% solution (approx. 0.04 mg/kg) and 5% solution (approx. 0.4 mg/kg). Drug concentrations were determined in plasma and various eye tissues on days 1, 16, and 30, and on day 59, i.e. on day 29 of the follow-up period. Bisoprolol concentrations in plasma and most eye tissues were considerably higher after oral than after conjunctival treatment. The highest tissue concentrations were observed in the iris (+ciliary body) and retina (+choroid) with tissue/plasma concentration ratios between 100 and 150 after oral and 1000 to 3000 after conjunctival instillation (5% solution). In plasma no accumulation of the drug was observed which is in accordance with its plasma half-life of 4 to 5 h. In contrast to this, concentrations in the iris and retina increased from day 1 to day 16 and 30 by 3 to 8 times and the half-life of bisoprolol in these tissues was estimated to be between 3 to 5 days.
Bühring
K U
KU
Institut für Toxikologie, Darmstadt, FRG.
Metallinos
A
A
Jakobs
N
N
von Landenberg
F
F
Merck
E
E
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D017298:Bisoprolol; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva; D004285:Dogs; D004333:Drug Administration Routes; D005123:Eye / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D008297:Male; D011412:Propanolamines / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D017298:Bisoprolol