Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were selected from Thailand's National List of Essential Medicine 2022 for potential DDI analysis by Micromedex and Drugs.com. From these databases, 488 potential DDIs were identified. There were 271 and 434 DDI pairs based on Micromedex and Drugs.com, respectively. Among these DDIs, 77 pairs were labeled as contraindicated or major by both databases. The most common mechanisms for these serious interactions are cytochrome P450 (CYP) inhibition (45%), CYP induction (19%), and QT interval prolongation (7.8%). Based on Fleiss' kappa (0.073), there was only slight agreement of the DDI severity classifications between these two databases. In conclusion, a large number of potential DDIs were detected among frequently prescribed medications for long COVID. Health care providers should be aware of these DDIs, particularly those that are deemed as contraindicated or major. These DDIs are most likely to cause significant adverse events in patients with long COVID because polypharmacy is common.

Absolute oral bioavailability and possible metabolic pathway of panduratin A from Boesenbergia rotunda extract in beagle dogs.

CONTEXT: Attempts are ongoing to develop medications to fight against the COVID-19 pandemic. Our previous study revealed the in vitro anti-SARS-CoV-2 activity of fingerroot [Boesenbergia rotunda (L.) Mansf. (Zingiberaceae)] and its phytochemical, panduratin A. OBJECTIVE: To investigate the pharmacokinetic profiles of panduratin A as a pure compound and in a fingerroot extract formulation in beagle dogs. MATERIALS AND METHODS: A total of 12 healthy dogs were randomly divided into three groups, a single dose of 1 mg/kg panduratin A by intravenous and multiple doses of 5 and 10 mg/kg panduratin A fingerroot extract formulation by oral administration for seven consecutive days. The plasma concentration of panduratin A was determined by LCMS. RESULTS: The peak concentrations of a single dose of 5 and 10 mg/kg panduratin A fingerroot extract formulation were 12,416 ± 2,326 and 26,319 ± 8,221 µg/L, respectively. Increasing the oral dose of fingerroot extract formulation, equivalent to panduratin A 5-10 mg/kg, showed dose proportionality, with an approximately 2-fold increase in Cmax and AUC. The absolute oral bioavailability of panduratin A in the fingerroot extract formulation was approximately 7-9%. The majority of panduratin A was biotransformed into several products via oxidation and glucuronidation, and predominantly excreted via the faecal route. CONCLUSION: The oral formulation of fingerroot extract was safe in beagle dogs, and increasing dose showed dose proportionality in terms of the systemic exposure of panduratin A. This information will support the phytopharmaceutical product development of fingerroot extract against the COVID-19 pandemic.

Drug-Herb Interactions among Thai Herbs and Anticancer Drugs: A Scoping Review.

More than half of Thai patients with cancer take herbal preparations while receiving anticancer therapy. There is no systematic or scoping review on interactions between anticancer drugs and Thai herbs, although several research articles have that Thai herbs inhibit cytochrome P450 (CYP) or efflux transporter. Therefore, we gathered and integrated information related to the interactions between anticancer drugs and Thai herbs. Fifty-two anticancer drugs from the 2020 Thailand National List of Essential Medicines and 75 herbs from the 2020 Thai Herbal Pharmacopoeia were selected to determine potential anticancer drug-herb interactions. The pharmacological profiles of the selected anticancer drugs were reviewed and matched with the herbal pharmacological activities to determine possible interactions. A large number of potential anticancer drug-herb interactions were found; the majority involved CYP inhibition. Efflux transporter inhibition and enzyme induction were also found, which could interfere with the pharmacokinetic profiles of anticancer drugs. However, there is limited knowledge on the pharmacodynamic interactions between anticancer drugs and Thai herbs. Therefore, further research is warranted. Information regarding interactions between anticancer drugs and Thai herbs should provide as a useful resource to healthcare professionals in daily practice. It could enable the prediction of possible anticancer drug-herb interactions and could be used to optimize cancer therapy outcomes.

Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-type and Mutant Colorectal Cancer.

Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone ≈ dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and γH2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via BAX, BIM, and caspase-9 as the main cell death pathway. Interestingly, the compounds were equally effective in p53-wild-type and p53-mutant CRC cells. Finally, the cytotoxic activity of the merosesquiterpenes was corroborated in intestinal tumor organoids, emphasizing their potential for CRC chemotherapy.

Quintaquinone, a Merosesquiterpene from the Yellow Sponge Verongula cf. rigida Esper.

A chemical investigation of the sponge Verongula cf. rigida led to the isolation of 13 merosesquiterpenes, among which quintaquinone (2), 5-epi-nakijiquinone L (3), and 3-farnesyl-2-hydroxy-5-methoxyquinone (4) were isolated and reported here for the first time. Particularly, compound 2 is the first member of merosesquiterpenes with a polyketide side chain substituted on C-19. All of the isolated compounds were examined for steroid 5α-reductase inhibitory activity. Cyclospongiaquinone 1 (5) showed a strong activity in the same range as that of standard finasteride.