Adinazolam pharmacokinetics and behavioral effects following administration of 20?60 mg oral doses of its mesylate salt in healthy volunteers

Jc, Fleishaker; Jp, Phillips

doi:10.1007/bf00634449

Cited by 22 publications

(17 citation statements)

References 15 publications

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“…administration of doses ranging from 5 to 20 mg (30-33), p.o. administration of immediate release (IR) formulations of doses ranging from 15 to 60 mg (31,32,(34)(35)(36)(37)(38)(39), and p.o. administration of sustained release (SR) formulations of doses ranging from 15 to 60 mg (32,(38)(39)(40).…”

Section: Adinazolammentioning

confidence: 99%

“…The in vivo PD data (sedation scores) were reported for p.o. IR formulations of doses ranging from 20 to 60 mg (34,36,38,39), and a 60-mg p.o. SR formulation.…”

Section: Adinazolammentioning

confidence: 99%

“…administration (31,(33)(34)(35) of doses ranging from 5 to 20 mg. The fitted PK parameters for these i.v.…”

Section: Adinazolammentioning

confidence: 99%

“…The fitted P eff and FPE values were then used in the simulations of all remaining oral doses. The PDPlus™ module of GastroPlus was then used to fit therapeutic PD response (mean sedation score) with the Cptime profiles of adinazolam (34). GastroPlus simulations were then used to predict the Cp-time profile and PD response profiles for release profiles with different release rates.…”

Section: Adinazolammentioning

confidence: 99%

“…doses of adinazolam (20 and 40 mg) were used to fit a PD model to reported sedation score profiles (34). The performance of the model was verified by predicting the 60-mg IR and SR dose (Fig.…”

Section: Adinazolammentioning

confidence: 99%

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Prediction of Modified Release Pharmacokinetics and Pharmacodynamics from In Vitro, Immediate Release, and Intravenous Data

Lukáčová

Woltosz

Bolger

2009

AAPS J

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Abstract. The aim of this study was to demonstrate the value of mechanistic simulations in gaining insight into the behaviors of modified release (MR) formulations in vivo and to use the properly calibrated models for prediction of pharmacokinetics (PK) and pharmacodynamics (PD). GastroPlus TM (Simulations Plus, Inc.) was used to fit mechanistic models for adinazolam and metoprolol that describe the absorption, PK, and PD after intravenous (i.v.) and immediate release (IR) oral (p.o.) administration. The fitted model for adinazolam was then used to predict the PD profile for a MR formulation and to design a new formulation with desired onset and duration of action. The fitted metoprolol model was used to gain insight and to explain the in vivo behaviors of MR formulations. For each drug, a single absorption/PK model was fitted that provided simulated plasma concentration-time profiles closely matching observed in vivo profiles across several different i.v. and p.o doses. Sedation score profiles of adinazolam were fitted with an indirect PD model. For metoprolol, the fitted absorption/ PK model for IR p.o. doses was used to select in vitro dissolution conditions that best matched the in vivo release of MR doses. This model also explained differences in exposure after administration of MR formulations with different release rates. Mechanistic absorption/PK models allow for detailed descriptions of all processes affecting the two drugs' bioavailability, including release/dissolution, absorption, and intestinal and hepatic first pass extraction. The insights gained can be used to design formulations that more effectively overcome identified problems.

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Section: Adinazolammentioning

confidence: 99%

“…The in vivo PD data (sedation scores) were reported for p.o. IR formulations of doses ranging from 20 to 60 mg (34,36,38,39), and a 60-mg p.o. SR formulation.…”

Section: Adinazolammentioning

confidence: 99%

“…administration (31,(33)(34)(35) of doses ranging from 5 to 20 mg. The fitted PK parameters for these i.v.…”

Section: Adinazolammentioning

confidence: 99%

Section: Adinazolammentioning

confidence: 99%

Section: Adinazolammentioning

confidence: 99%

See 3 more Smart Citations

Prediction of Modified Release Pharmacokinetics and Pharmacodynamics from In Vitro, Immediate Release, and Intravenous Data

Lukáčová

Woltosz

Bolger

2009

AAPS J

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Effect of food on the bioavailability of adinazolam from a sustained release formulation: Effect of meal timing and lack of dose dumping

Fleishaker

Phillips

Lau

1990

Biopharm & Drug Disp

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Food effects on adinazolam absorption from sustained release (SR) adinazolam mesylate tablets were assessed in 28 healthy male volunteers. Subjects received 15 mg SR tablets, 15 mg immediate release tablets, 15 mg oral solution, administered after an overnight fast, and 15mg SR tablets after a high fat breakfast. Treatments were administered in a crossover design. Plasma adinazolam and N-desmethyladinazolam (NDMAD) concentrations were determined by HPLC. Adinazolam and NDMAD AUC values were unaffected by food. C, , , for SR tablets was increased 33 per cent and 18 per cent for adinazolam and NDMAD, respectively, when administered postprandially. T,,, occurred later in the fed state; no dose dumping was observed. Meal timing effects on adinazolam absorption from SR tablets were assessed in 24 healthy subjects, who received 30 mg SR tablets 1 h before, 0.5 h after, 2 h after a high fat meal, and in the fasted state. Postprandial administration had no effect on AUC, but resulted later and higher adinazolam and NDMAD C, , , . Differences in these values were less than 11 per cent. Administration of SR tablets before meals yielded C,,, and T,,, values which were similar to the fasted state. Results suggest that meal timing does not substantially affect adinazolam absorption from the SR tablet.

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The emergence of new psychoactive substance (NPS) benzodiazepines: A review

Manchester

Lomas

Waters

et al. 2017

Drug Testing and Analysis

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The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased.Some of these benzodiazepines have only been patented, some of them have not been previously synthesised, and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s, many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are novel psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. This review collates the available information on these benzodiazepines and provides a starting point for the further investigation of their pharmacokinetics which is clearly required.

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Adinazolam pharmacokinetics and behavioral effects following administration of 20?60 mg oral doses of its mesylate salt in healthy volunteers

Cited by 22 publications

References 15 publications

Prediction of Modified Release Pharmacokinetics and Pharmacodynamics from In Vitro, Immediate Release, and Intravenous Data

Prediction of Modified Release Pharmacokinetics and Pharmacodynamics from In Vitro, Immediate Release, and Intravenous Data

Effect of food on the bioavailability of adinazolam from a sustained release formulation: Effect of meal timing and lack of dose dumping

The emergence of new psychoactive substance (NPS) benzodiazepines: A review

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