Effects of itraconazole and carbamazepine on the pharmacokinetics of nirmatrelvir/ritonavir in healthy adults.

Aims: The objective of this study was to evaluate the effects of a strong cytochrome P450 family (CYP) 3A4 inhibitor (itraconazole) and inducer (carbamazepine) on the pharmacokinetics and safety of nirmatrelvir/ritonavir.

Methods: Pharmacokinetics were measured in two phase 1, open-label, fixed-sequence studies in healthy adults. During Period 1, oral nirmatrelvir/ritonavir 300 mg/100 mg twice daily was administered alone; during Period 2, it was administered with itraconazole or carbamazepine.

Metabolism and Excretion of Nirmatrelvir in Humans Using Quantitative Fluorine Nuclear Magnetic Resonance Spectroscopy: A Novel Approach for Accelerating Drug Development.

Typically human absorption, distribution, metabolism, and excretion (ADME) studies are executed using radiolabeled (e.g., carbon-14) material, the synthesis of which is a time-consuming activity.

Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir.

Coronavirus disease 2019 (COVID-19) is a continued leading cause of hospitalization and death. Safe, efficacious COVID-19 antivirals are needed urgently. Nirmatrelvir (PF-07321332), the first orally bioavailable, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) M inhibitor against the coronaviridae family, has demonstrated potent preclinical antiviral activity and benign safety profile.

From structure to the dynamic regulation of a molecular switch: A journey over 3 decades.

It is difficult to imagine where the signaling community would be today without the Protein Data Bank. This visionary resource, established in the 1970s, has been an essential partner for sharing information between academics and industry for over 3 decades. We describe here the history of our journey with the protein kinases using cAMP-dependent protein kinase as a prototype.

Serotonin and vasotocin function in territoriality.

This ethopharmacological investigation comprised a long-term field study that examined the function of serotonergic and vasotonergic systems in territoriality. Adult territorial and non-territorial (silent) male coquí frogs (Eleutherodactylus coqui) were injected (IP) with either arginine vasotocin (AVT) or one of two serotonin agonists, 5-HT selective agonist, (±) DOI - [(±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane], or 2) the 5-HT selective agonist, 8-OH-DPAT - [(±)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene]. Control groups received saline injections.