title: Pharmacokinetic interactions of timolol with vasodilating drugs, food and phenobarbitone in healthy human volunteers.
abstract: Pharmacokinetic interactions of oral timolol maleate 10 mg, with food (3566 kJ), single oral doses of prazosin 1 mg and dihydralazine 25 mg, and with a 1 week pretreatment with phenobarbitone 100 mg daily were examined in a randomized crossover study in 12 healthy volunteers. After fasting, the peak level (Cmax = 29.1 +/- 3.2 ng/ml; mean +/- SEM) was reached at 1.3 +/- 0.1 h (Tmax). The total area under the serum concentration-time curve (AUC0-infinity) was 154.4 +/- 33.8 ng x h/ml, total clearance (Cltot) 751.5 +/- 90.6 ml/min, renal clearance (Clren) 97.2 +/- 10.1 ml/min, elimination half-life (t1/2) 2.9 +/- 0.3 h and 24-h recovery in urine (X0u-24) 11.1 +/- 1.4% of the dose. Food and prazosin did not significantly affect the fate of timolol maleate. Dihydralazine enhanced Cmax (38.2 +/- 4.6 ng/ml) only when compared to phenobarbitone treatment, and did not affect any other parameters. Phenobarbitone pretreatment somewhat lowered Cmax (25.5 +/- 3.9 ng/ml), AUC0-infinity (117.5 +/- 22.1; p less than 0.05 vs food) and X0u-24 (8.7 +/- 1.2%), evidently by increasing Cltot (957.5 +/- 116.9 ml/min; p less than 0.05 vs food), but it did not affect Clren. It is concluded that the pharmacokinetics of timolol maleate can be altered to a limited extent in opposite directions by dihydralazine and phenobarbitone.
mesh_terms: D000328:Adult; D001682:Biological Availability; D004078:Dihydralazine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005502:Food; D006801:Humans; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism*; D013999:Timolol / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D011412:Propanolamines; D014665:Vasodilator Agents; D013999:Timolol; D004078:Dihydralazine; D011224:Prazosin; D010634:Phenobarbital