A single intravenous dose of DMT fully suppresses alpha brain wave power, partially suppresses beta power, and increases signal diversity (Lempel-Ziv complexity) in the EEG of 13 healthy volunteers. The concentration needed to reach half of the maximum effect (EC50) was 71 nM for alpha suppression, 137 nM for beta suppression, and 54 nM for increased complexity. Alpha suppression showed the least variability between individuals (29%), while beta suppression and complexity varied widely (75% and 77%). These quantified relationships between DMT blood levels and brain activity may help select appropriate doses and response markers in future clinical research.
S65487, a drug targeting the Bcl2/Bim protein complex implicated in cancer cell survival, was studied using pharmacokinetic/pharmacodynamic modeling. At a 1200 mg dose, simulations predicted a 97.6% maximum reduction in the formation of the Bcl2/Bim complex. A microdose study in healthy volunteers showed substantially different pharmacokinetic parameters compared to therapeutic doses in cancer patients, indicating slightly nonlinear drug behavior. The most plausible explanation was nonlinearity in drug disposition, modeled via a Michaelis-Menten approximation of target-mediated drug disposition. This optimized model reduced the discrepancy in describing microdose exposure from 5-fold to 1-fold, without affecting therapeutic dose descriptions, enabling better extrapolation from microdose to therapeutic dose results.