Expert Opinion on Drug Metabolism & Toxicology
April 4, 2013
Graham Lappin, Robert J. Noveck, Tal Burt
97 citations
Microdosing uses inherently safe, sub-pharmacologic doses of drug to acquire exploratory pharmacokinetic data in humans early in drug development. A decade after the first microdose data publication, evidence suggests microdosing may predict human pharmacokinetics better than alternative methods. Combining microdosing with physiologically based modeling could yield more reliable future predictions. The concept has been applied to drug-drug interactions, polymorphism, and assessing drug concentrations over time at the site of action. Microdosing may offer additional unanticipated benefits not yet fully realized.
Expert Opinion on Drug Metabolism & Toxicology
November 28, 2008
Graham Lappin, R Colin Garner
89 citations
A review of 18 drugs found that 15 showed linear pharmacokinetics, meaning their drug concentration profiles at a microdose (≤100 micrograms) fell within a factor of two of those at a therapeutic dose. This supports the use of microdosing in Phase 0 trials to predict how a drug will behave at clinically relevant doses, helping to select candidates for further testing.
Expert Opinion on Drug Metabolism & Toxicology
March 31, 2020
Esther Papaseit, Clara Pérez‐mañá, Marta Torrens et al.
34 citations
MDMA (ecstasy) is a widely used recreational stimulant. Users often combine it with other drugs to enhance effects, reduce toxicity, or manage comedowns, which increases the risk of severe toxicity. This review covers known interactions between MDMA and other pharmaceuticals or drugs of abuse, offering clinical recommendations. The authors note that few published studies exist and documented clinically significant interactions are scarce. Experimental evidence shows that interactions are especially relevant when MDMA is taken with drugs metabolized by the CYP2D6 enzyme, due to MDMA's inhibitory effect, and during repeated MDMA use.
Expert Opinion on Drug Metabolism & Toxicology
June 18, 2021
M. Luz, D. Mash
30 citations
Ibogaine, a psychoactive alkaloid from the West African shrub Tabernanthe iboga, has a history of use by indigenous cultures for fatigue, hunger, and religious ceremonies. First isolated in 1901, it was marketed in France until 1970 as a neuromuscular stimulant. Since the 1960s, anecdotal reports have suggested benefits for treating opioid abuse, though it was later classified as a Schedule I substance by the FDA. While the benefit-risk ratio for opioid withdrawal under medical supervision appears favorable, published reports of drug-related deaths and safety concerns continue to impede development.
Expert Opinion on Drug Metabolism & Toxicology
January 5, 2018
Esther Papaseit, Marta Torrens, Clara Pérez‐mañá et al.
20 citations
MDMA (ecstasy) produces amphetamine-like euphoria and well-being, increases empathy, and induces pro-social effects that drive recreational use and suggest therapeutic potential. This review examines interindividual differences in MDMA's pharmacodynamics, focusing on sex-gender, race-ethnicity, genetic differences, interactions, acute toxicity, and therapeutic use. Acute MDMA effects are more pronounced in women than men. Very limited data exist on race-ethnicity effects. MDMA metabolism involves polymorphic enzymes that slightly alter plasma concentrations and effects. The small number of subjects in acute-effect trials limits evaluation of interindividual factors and prevents clear conclusions about their influence, which should be considered in therapeutic studies.