Summary
Eight healthy volunteers were given single i.v. and oral doses of clonazepam (2 mg). The disposition curves after i.v. administration showed a biexponential decline and the data were applied to a two-compartment open model. The volume of distribution ((Vd)β) ranged between 1.5 and 4.4 l/kg and the plasma half-life (t1/2) between 19 and 60 hours. Absorption after oral administration was fast, with peak plasma concentrations within 4 hours in all subjects. Five of the subjects received repeated oral doses of clonazepam 0.5 mg bid for 15 days. The plasma level during steady state (estimated as Cmin within the dose interval) could be predicted from the constants A, B, α and β obtained in the single dose study with a coefficient of variation of 6%. The plasma half-lives after cessation of the subchronic dosing were of the same magnitude as after single doses.
Similar content being viewed by others
References
Berlin, A., Siwers, B., Agurell, S., Hiort, A., Sjöqvist, F., Ström, S.: Determination of bioavailability of diazepam in various formulations from steady state plasma concentration data. Clin. Pharmacol. Ther.13, 733–744 (1972)
Boxer, G.E., Jelinek, V.C., Tompsett, R., Du Bois, R., Edison. A.: Streptomycin in the blood; chemical determinations after single and repeated intramuscular injections. J. Pharm. exp. Ther.92, 226–235 (1948)
Eschenhof, E.: Untersuchungen über das Schicksal des Antikonvulsivums Clonazepam im Organismus der Ratte, des Hundes und des Menschen. Arzneimittel-Forsch.23, 390–400 (1973)
Gastaut, H.: Propriétés anti-épileptiques exceptionelles d'une benzodiazepine nouvelle, le Ro 5-4023. Vie méd.51, 5175–5788 (1970)
Gibaldi, M., Nagashima, R., Levy, G.: Relationship between drug concentration in plasma or serum and amount of drug in the body. J. pharm. Sci.58, 193–197 (1969)
Kaplan, S.A., Jack, M.L., Alexander, K., Weinfeld, R.E.: Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. J. pharm. Sci.62, 1789–1796 (1973)
Kaplan, S.A., Alexander, K., Jack, M.L., Puglisi, C.V., de Silva, J.A.F., Lee, T.L., Weinfeld, R.E.: Pharmacokinetic profiles of clonazepam in dog and humans and of flunitrazepam in dog. J. pharm. Sci.63, 527–532 (1974)
Rescigno, A., Segre, G.: Drug and tracer kinetics. Waltham, Mass.: Blaisell 1966
Riegelman, S., Loo, J.C.L., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. pharm. Sci.57, 117–123 (1968)
Riggs, D.S.: The mathematical approach to physiological problems. Baltimore, Md.: Williams & Wilkins 1967
Teorell, T.: Kinetics of distribution of substances administered to the body. II. The intravascular modes of administration. Arch. intern. Pharmacodyn.57, 226–240 (1937)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Berlin, A., Dahlström, H. Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration. Eur J Clin Pharmacol 9, 155–159 (1975). https://doi.org/10.1007/BF00614012
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00614012