Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 237 - 237
Published: Feb. 12, 2025
Background: As cannabis becomes legal in several U.S. states, the risk of THC-induced tachycardia increases. This study aimed to develop and verify a physiologically based pharmacokinetic-pharmacodynamic (PBPK-PD) model assess impact THC its active metabolite, 11-hydroxy-THC (11-OH-THC), on heart rate healthy adults. Methods: A PBPK-PD for intravenous (IV) 11-OH-THC administration was first developed. Secondly, IV THC, combined with metabolized 11-OH-THC, established, verified, validated. Direct PD models driven by plasma, brain, concentrations predicted using our previously verified PBPK were tested development. Finally, risks at rest condition from various doses oral inhaled simulated 500 individuals aged 18-65 years, sex ratio 1:1 baseline 70 beats per minute. Results: The best described direct nonlinear Emax sum total their effect compartments linked compartments. In 42 dosing regimens ranging 2 69.4 mg, 97% observed rates or changes following fell within 5th 95th percentiles model-predicted values. Similarly, two doses, 93% observations this range. Simulations indicated that half population would experience 60 mg 15 administration, respectively. specific conditions should be interpreted caution. Conclusions: Our successfully describes adults after IV, oral, administration. provides tool predict effects primary metabolite rates, offering valuable insights assessing both clinical recreational use.
Language: Английский