The pharmaceutical sector is increasingly prioritizing the improvement of predictive modeling for human pharmacokinetics (PK) related to drug candidates, aiming to reduce costs and enhance efficiency in research and development. Most of these initiatives have focused on predicting drug absorption after oral administration, which is the preferred method for drug delivery. Despite significant progress in this field, accurately forecasting the fraction of the dose that is absorbed (Fa) continues to pose a considerable challenge. In recent years, multi-compartment and transit models have become increasingly popular because of their effectiveness. However, these models treat the stomach as a single compartment with a fixed pH, which can lead to inaccuracies in estimating the solubilization of basic drugs in the stomach under certain conditions, ultimately resulting in false results. To address the above challenge, a kinetic stomach pH calculator that converts a pH-time profile to a single pH input has been introduced, yet it remains inadequate for drugs with low base pKa values such as quazepam. This article explored the integration of pH-dependent solubility into the stomach compartment on the previously published kinetic model, demonstrating its potential to improve the predictive accuracy regarding the impact of food on quazepam. This innovative method has demonstrated greater effectiveness in assessing the impact of food on basic drugs with low pKa. It is suggested that this revised approach may prove advantageous for all models encountering similar difficulties.

C9-methylated quazepam 1 was prepared, and its physicochemical properties were investigated. The atropisomers of 1 were isolated as (a[1]R, a[2]S) and (a[1]S, a[2]R) isomers. Their absolute configurations were determined based on ECD spectra in comparison with those calculated using the time-dependent density functional theory. Preliminary examination of affinity for the GABAA receptor revealed that the (a[1]R, a[2]S) isomer of 1 possessed higher activity than its antipode (a[1]S, a[2]R) isomer. The active configuration of C9-methylated quazepam 1 is the same as that of 1,4-benzodiazepin-2-ones.

No information is available on the long-term use of quazepam during breastfeeding. Because the drug and metabolites could accumulate in the breastfed infant, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.

Quazepam is an orally available benzodiazepine used to treat insomnia. As with most benzodiazepines, quazepam therapy has not been associated with serum aminotransferase or alkaline phosphatase elevations, and clinically apparent liver injury from quazepam has not been reported and must be very rare, if it occurs at all.

Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.

Insomnia is a prevalent disorder that affects over one-third of the U.S. population to varying degrees and is highly disruptive towards quality of life. Pharmacological treatments for insomnia include benzodiazepines (BZs) and the non-BZ 'Z-drugs' (zolpidem, zaleplon, eszopiclone, zopiclone), which are amongst the most widely prescribed medications. Yet, these agents can produce adverse effects such as tolerance to the hypnotic effect, rebound insomnia, next-day residual drowsiness, as well as amnesia and complex behaviours such as sleep-walking, sleep-eating and sleep-driving. Quazepam, one of the five BZ approved for treatment of insomnia, was recently relaunched to the U.S. market in 2016 and is distinguished amongst hypnotic BZ by unique pharmacological characteristics including selectivity for sleep-promoting α1-subunit containing γ-aminobutyric acid (GABA-A) receptors and a significantly lower relative receptor binding affinity. These features likely drive the decreased rate of adverse events seen clinically with quazepam, such as tolerance, rebound insomnia and amnesic behaviours, compared with other BZ. Given the recent reintroduction of quazepam as a pharmacotherapeutic option, and the lack of head-to-head comparative trials against newer agents, the purpose of this review is to provide an update on distinguishing features of quazepam with regard to its pharmacology, pharmacokinetics, sleep efficacy and potential adverse effects compared to other agents used for insomnia.