Summary
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−∞) was 154.4±33.8 ng×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 (X 0–24u ) 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−∞ (117.5±22.1;p<0.05 vs food) and X 0–24u (8.7±1.2%), evidently by increasing Cltot (957.5±116.9 ml/min;p<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.
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Mäntylä, R., Männistö, P., Nykänen, S. et al. Pharmacokinetic interactions of timolol with vasodilating drugs, food and phenobarbitone in healthy human volunteers. Eur J Clin Pharmacol 24, 227–230 (1983). https://doi.org/10.1007/BF00613822
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DOI: https://doi.org/10.1007/BF00613822