Drug Metabolism and Disposition
December 3, 2005
Suresh K. Balani, N. Nagaraja, Mark G. Qian et al.
61 citations
Conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS) can characterize pharmacokinetics of nonlabeled drugs at a microdose of 1 microg/kg in rats, offering a more accessible alternative to accelerator mass spectrometry (AMS) for microdosing studies. For fluconazole and tolbutamide, exposure was linear between the microdose and doses 1000-fold higher, supporting LC-MS/MS's utility in human microdosing. However, for an investigational compound MLNX, pharmacokinetics in rats were nonlinear, suggesting its microdose pharmacokinetics in humans might not reflect therapeutic doses. These findings indicate LC-MS/MS is adequate for microdose pharmacokinetic assessment in humans, though nonlinearity in some compounds may limit predictability.
Drug Metabolism and Disposition
October 19, 2013
Marta Concheiro, Michael H. Baumann, Karl B. Scheidweiler et al.
32 citations
MDMA, an illicit drug with potential clinical use for PTSD and anxiety, shows nonlinear accumulation in male rats due to metabolic autoinhibition. After doses of 2.5, 5, and 10 mg/kg, MDMA and its metabolite MDA increased more than proportionally with dose, while other metabolites remained constant. Serotonin syndrome severity correlated with MDMA concentrations, and core temperature correlated with MDA concentrations, suggesting distinct mechanisms for behavioral and hyperthermic effects. At 2.5 mg/kg, MDMA Cmax was 164 ± 47.1 ng/ml, with HHMA and HMMA as major metabolites and less than 20% converted to MDA. These findings, given similarities to human pharmacokinetics, support using rat data at clinically relevant doses.
Drug Metabolism and Disposition
September 1, 1978
L. Demisch, Peter Kaczmarczyk, Nikolaus Seiler
14 citations
After people took 400 mg of mescaline sulfate, a metabolite called 3,4,5-trimethoxybenzoic acid was found in their urine and identified using gas chromatography-mass spectrometry. This substance appeared in much smaller amounts than the better-known metabolite 3,4,5-trimethoxyphenylacetic acid. The finding suggests that the body processes mescaline through an additional, minor chemical pathway that produces an anionic compound, though its overall role in mescaline metabolism is limited.
Drug Metabolism and Disposition
March 1, 1975
Nandkumar S. Shah, Kanhaiya R. Shah, R.s. Lawrence et al.
6 citations
Younger rats accumulate and retain mescaline in their organs more than adults, with the highest brain uptake in newborns decreasing steadily with age. The blood-brain barrier for mescaline develops gradually and remains partially permeable in adults. Deaminated metabolite levels were also measured in brain, liver, heart, spleen, lung, and kidney.