M.L. Jack

Pharmacokinetic and biopharmaceutic profile of chlordiazepoxide HCl in healthy subjects: Single-dose studies by the intravenous, intramuscular, and oral routes

Single 30- mg doses of chlordiazepoxide HCl were administered to six healthy human subjects by the intravenous, oral, and intramuscular routes. Plasma concentration- time curves following intravenous administration were satisfactorily described by a biexponential equation consistent with a two-compartment open model system. Mean values of half-lives for the so-called distribution and elimination phases were 0.252 and 9.39 hr, respectively. The mean values for the volume of the central compartment (V1) and volume of distribution

Relationships between CSF drug concentrations, receptor binding characteristics, and pharmacokinetic and pharmacodynamic properties of selected 1,4-substituted benzodiazepines

(V_{d_\beta } )

Utility of Bioavailability Studies in Drug Development

were 18.0 and 30.9% of body weight, respectively. Following oral administration, the drug was rapidly and completely absorbed. Absorption was first order (t1/2≈27 min), and three of the six subjects showed a discernible lag time of approximately 20 min. Drug absorption following intramuscular administration was comparatively slow. A two- compartment “muscle model” comprised of precipitated and solubilized drug in the muscle was found to satisfactorily characterize the absorption process following administration by this route.

Pharmacokinetic Profile of Diazepam in Man following Single Intravenous and Oral and Chronic Oral Administrations

Bromazepam appears to be completely absorbed in man. The intact drug was eliminated from the blood with a mean half-life of 11.9 hr. Predictable steady-state blood levels are maintained on multiple daily dosing.

Pharmacokinetic profiles of clonazepam in dog and humans and of flunitrazepam in dog.

SummaryPharmacokinetic profiles of the 1,4-substituted benzodiazepines are defined by their absorption, distribution, metabolism, and excretion characteristics. An ability to cross the blood- brain barrier and the onset of pharmacological activity have been associated with the physiochemical properties of the benzodiazepines. In addition, drug concentrations in the CSF correlate with the unbound drug concentrations in blood or plasma. Duration of pharmacological activity of the benzodiazepines in humans is associated with the affinity of these compounds for the benzodiazepine receptors in human brain. Therefore, benzodiazepines with high affinity for the benzodiazepine receptor sites in human brain tend to exhibit prolonged half-lives of elimination from the CSF which correlate with the prolonged duration of clinical and pharmacological effects and lower therapeutic doses of these drugs in vivo.

Pharmacokinetic Profile of Trimethoprim-Sulfamethoxazole in Man

Eight healthy male volunteers received chlordiazepoxide HCl orally at a dosage of 10 mg every 8 hr over a period of 21 days. On day 22, the regimen was changed to 30 mg every 24 hr for an additional 15 days. Plasma concentrations of chlordiazepoxide and its metabolites desmethyl-chlordiazepoxide, demoxepam, and desoxydemoxepam were measured during 14 of the 36 treatment days. Chlordiazepoxide plasma concentration- time data were consistent with first-order absorption and complete bioavailability. The harmonic mean absorption half-life was 12.3 min. Disposition of chlordiazepoxide was described by a two-compartment open model with a harmonic mean terminal exponential half-life of 10.1 hr. Average steady — state plasma levels of chlordiazepoxide, desmethylchlordiazepoxide, and demoxepam were approximately 0.75, 0.54, and 0.36 μg/ml, respectively.

Bumetanide: Radioimmunoassay and pharmacokinetic profile in humans

AbstractA sequentially designed drug development program considering bioavailability studies in relation to the many disciplines involved in drug development will have the greatest potential for success.