Summary
The pharmacokinetics of timolol, after oral administration of single 20 mg doses to healthy subjects, has been studied using an original electron beam ionization GLC-mass spectrometry technique with computer — controlled multiple ion detection. This method of mass fragmentography, tested with propranolol as an internal standard, permitted the measurement of timolol concentrations as low as 1 ng/ml with good precision and accuracy. It enabled the plasma level to be followed up to the twelfth hour after treatment. Individual variation was observed in bioavailability; the peaks plasma concentration (Cmax) of 50 to 103 ng/ml being achieved at different times(0.5–3 h). The residual level after 12 h differed greatly between the subjects (0.8 to 7.2 ng/ml). The mean half-life of the terminal elimination phase was 2.62 ± 0.17 h. Extra-renal elimination (metabolic and biliary) represented the main route of elimination, with a renal to body clearance ratio of 0.123. This level paralleled the percentage of unaltered timolol excreted in urine 24 h after its administration.
Similar content being viewed by others
References
Tocco DJ, Duncan AEW, Deluna FA, Hucker HB, Gruber UF, Wandenheuvel WJA (1975) Physiological disposition and metabolism of timolol in man and laboratory animals. Drug Metab Dispos 3: 361–370
Lowenthal DT, Pitone JM, Affrime MB, Shirk J, Busby P, Kim KE, Nancarrow J, Swartz C, Onesti G (1978) Timolol kinetics in chronic renal insufficiency. Clin Pharmacol Ther 23: 606–615
Else OF, Sorenson H, Edwards IR (1978) Plasma timolol levels after oral and intravenous administration. Eur J Clin Pharmacol 14: 431–434
Gomeni C, Gomeni R (1978) Interactive graphic package for pharmacokinetic analysis. Comput Biomed Res 11: 345–361
Ainsh J Mc (1977) Clinical pharmacokinetics of Atenolol. Postgrad Med J 53 (Suppl 3): 74–78
Conway JF, Fitzgerald JD, Ainsh JMc, Rowlands RJ, Simpson WT (1976) Human pharmacokinetics and pharmacodynamic studies on atenolol (I. C. 66082), a new cardioselective β adrenoceptor blocking drug. Br J Clin Pharmacol 3: 267–272
Malangeau P (1978) Aperçu sur la chimie des β bloquants. Actual Pharmacol 149: 30–35
Winckle RA, Meffin PJ, Ricks WB, Harrison DC (1977) Acebutolol metabolite plasma concentration during chronic oral therapy. Br J Clin Pharmacol 4: 519–522
Vermeij P, El Sherbini Schepers M, Vanzwieten PA (1978) The disposition of Timolol in man. J Pharm Pharmacol 30: 53–55
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fourtillan, J.B., Courtois, P., Lefebvre, M.A. et al. Pharmacokinetics of oral timolol studied by mass fragmentography. Eur J Clin Pharmacol 19, 193–196 (1981). https://doi.org/10.1007/BF00561948
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00561948