Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans

  title={Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans},
  author={Silvio R. Bareggi and Giulio Truci and S Leva and Luigi Zecca and Rodolfo Pirola and Salvatore Smirne},
  journal={European Journal of Clinical Pharmacology},
SummarySix healthy, fasting volunteers were given single doses of chlordesmethyldiazepam by 1 mg i. v., or as drops or tablets. Chlordesmethyldiazepam and its metabolite, lorazepam, in multiple plasma samples and in urine collected for 120 h after each dose were determined by electron-capture GLC.Mean kinetic variables for intravenous chlordesmethyldiazepam were: volume of distribution, 1.71 l · kg−1; elimination half-life, 113 h; total clearance, 0.21 ml · min−1 · kg−1; cumulative excretion of… 

Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis

SummaryThe pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The

Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam

There is a need for caution in the administration of chlordesmethyldiazepam to patients with liver disease, as the elimination half-life was almost twice that in controls and volume of distribution was similar in patients and controls.

Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study.

A rapid, sensitive and specific LC-MS/MS method was developed and validated for quantifying chlordesmethyldiazepam (CDDZ or delorazepam), the active metabolite of cloxazolam, in human plasma and indicated bioequivalence since all ratios were as proposed by FDA and ANVISA.

Understanding the pharmacokinetics of anxiolytic drugs

A need for a more balanced assessment of the benefits and risks associated with benzodiazepine use, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment.

Rapid Improvement of Treatment-Resistant Major Depression During the Administration of Low-Dose Oxycodone.

3 cases of rapid TRD improvement during the administration of the μopiate agonist oxycodone, in patients with concomitant severe nociceptive pain are reported.



Pharmacokinetics and Bioavailability of Intravenous, Intramuscular, and Oral Lorazepam in Humans

Six healthy volunteers received single 2- and 4-mg doses of lorazepam by 5-min intravenous infusion, in tablet form by mouth in the fasting state, and by deltoid intramuscular injection in a six-way

Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam).

Data indicate that CDDZ is more slowly eliminated and less metabolized as age increases, and older patients improved significantly less than those of group 1 and had also an higher incidence of side-effects.

Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations.

The rate at which diazepam returns to the central compartment from the deep peripheral compartment, k31, was shown to be the rate-controlling factor in the elimination of diazepAM and in the formation of desmethyldiazepam.

Effect of a cocktail on diazepam absorption

Coadministration of diazepam with the ethanol cocktail tended to slow the rate ofdiazepam absorption, but did not influence the completeness of absorption, as well as the area under the 24-h plasma concentration curve, was nearly identical for the two conditions.

Clinical Pharmacokinetics of Diazepam

Based on kinetic data, a single administration of diazepam at night should be adequate for hypnotic and anxiolytic effects in most patients and measurement of blood levels is unnecessary.

Plasma levels of chlorodesmethyldiazepam in humans

Chlorodesmethyldiazepam (I) concentrations were followed for 72 h in the plasma of four volunteers given 2 mg of the drug orally. The drug appears to be well absorbed, reaching peak plasma levels of

Diazepam actions and plasma concentrations following ethanol ingestion

Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.

Novel application of proton nuclear magnetic resonance spectroscopy in the identification of 2'-chloronordiazepam metabolites in the dog.

A novel method is introduced to identify the 4'-hydroxy isomer 3, based on attributing different sets of NMR substituent effect parameters to hydroxyl groups, depending on whether these groups are meta or para to the benzodiazepinimine function.

On the hypnogenic and anticonvulsant activities of demethyldiazepam and chlordemethyldiazepam: time‐effect relations *

The time-effect relations of D M D Z and CI-DMDZ in tests evaluating their sleep-inducing and anticonvulsant activities are studied.