Clonazepam pharmacokinetics

Greenblatt, D.J., Miller, L.G., and Shader, R.I. (1987) Clonazepam pharmacokinetics, brain uptake, and receptor interactions. / Clin Psychiatry 48 Suppl 4-11. 

Benzodiazepines. The introduction of the benzodiazepines represented a significant advance in the treatment of panic disorder. In contrast to MAOIs and TCAs, the benzodiazepines begin to provide relief the very first day of treatment, and many patients experience a complete response by the end of the second week of therapy. All benzodiazepines should theoretically alleviate the symptoms of a panic attack at comparable doses, but the benzodiazepines of choice are alprazolam (Xanax, Xanax XR) and clonazepam (Klonopin). It likely is not coincidental that these two are among the highest potency benzodiazepines. However, they differ considerably from a pharmacokinetic standpoint. If clonazepam is the tortoise of benzodiazepines, then alprazolam is the hare. 

The speciflc clinical use of the numerous available benzodiazepines depends on their individual pharmacokinetic and pharmacodynamic properties. Drugs with a high affinity for the GABAa receptor (alprazolam, clonazepam, lorazepam) have high anxiolytic efficacy drugs with a short duration of action (temazepam) are used as hypnotics to minimise daytime sedative effects. Diazepam has a long half-life and duration of action and may be favoured for long-term use or when there is a history of withdrawal problems oxazepam has a slow onset of action and may be less susceptible to abuse. 

DeVane, C.L., Ware, M.R., and Lydiard, R.B. (1991) Pharmacokinetics, pharmacodynamics, and treatment issues of benzodiazepines alprazolam, adinazolam, and clonazepam. Psychophar-macol Bull 27 463-473. 

In a randomized, double-blind, placebo-controlled, crossover study in 13 subjects, sertraline did not affect the pharmacokinetics or pharmacodynamics of clonazepam (26). 

Yukawa E, Nonaka T, Yukawa M, Ohdo S, Higuchi S, Kuroda T, Goto Y. Pharmacoepidemiologic investigation of a clonazepam-carbamazepine interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients. J Clin Psychopharmacol 2001 21(6) 588-93. 

Colucci R, Glue P, Banfield C, Reidenberg P, Meehan J, Radwanski E, Korduba C, Lin C, Dogterom P, Ebels T, Hendriks G, Jonkman J, Affrime M. Effect of felbamate on the pharmacokinetics of clonazepam. Am J Ther 1996 3(4) 294-7. 

Studies on the pharmacokinetics of flunltrazepam (lb) in man, clonazepam (Ih) in rhesus monkeys, and triazolam (9a) in dogs have appeared. The metabolism of bromazepam (li) in rodents has been studied, and the major metabolic pathway is cleavage of the benzodiazepine ring at the - 2 and bonds with subsequent reduction and hydroxy-... 

PHARMACOKINETIC PROPERTIES Benzodiazepines are well absorbed orally, and peak plasma concentrations are usually reached within 1 hours. After intravenous administration, they redistribute in a manner typical of highly lipid-soluble agents (see Chapters 1 and 16). CNS effects develop rapidly but wane quickly as the drugs move to other tissues. Diazepam redistributes rapidly (fy of redistribution, -1 hour). The extent of binding of benzodiazepines to plasma proteins correlates with Upid solubriity, ranging from 99% for diazepam to -85% for clonazepam. 

Kaplan SA, Alexander K, Jack ML, Puglisi CV, DeSilva JAF, Lee TL and Wenfeld RE, Pharmacokinetic profiles of clonazepam in dog and... 

Since norclobazam retains some of the activity of clobazam the effects of carbamazepine probably have little clinical significance, and the case of carbamazepine toxicity appears to be isolated and is therefore probably of limited importance. The pharmacokinetic changes seen with clonazepam seem likely to be too small to be clinically significant, but this needs confirmation. 

Sjb 0, Hvidberg EF, Naestoft J, Lund M. Pharmacokinetics and side-effects of clonazepam and its 7-amino metabolite in man. EurJ Clin Pharmacol (1975) 8, 249-54. 

Assay of Underivatized Nitrazepam and Clonazepam in Plasma by Capillary Gas Chromatography Applied to Pharmacokinetics and Bioavailability Studies in Humans... 

---