Laevo-[1-³H]Methadone Disposition in Tolerant Dogs

Abstract

1. Following a subcutaneous dose (4mg/kg) of [3H]methadone, peak levels of drug occurred in plasma, tissues and selected areas of the central nervous system (CNS) 2h after injection in both non-tolerant and tolerant dogs. Highest concentrations of methadone were attained in bile and lung compared to other tissues. 2. Levels of methadone in plasma, tissue and CNS of tolerant and non-tolerant animals were not markedly different up to 8h after injection, but a much faster rate of egression of free drug (lower t1/2) was observed subsequently in tolerant dogs. 3. Peak levels of methadone in various areas of the CNS ranged between 2-7 (spinal cord) to 3-6 (thalamus) mug/g in non-tolerant and 3-0 -rebellum) to 4-1 (thalamus) mug/g in tolerant dogs 2h after injection. No marked accumulation of methadone occurred in selected areas of the CNS in spite of the persistence of drug in these areas. 4. The plasma protein electrophoretic profiles did not differ between control, non-tolerant and tolerant dogs. 5. Similar qualitative patterns of metabolites were observed in non-tolerant and tolerant dogs and the development of tolerance did not appear to modify the metabolic pathways of methadone.

Sensitive Fluorescence Assay ford,l‐Methadone

“…On the basis of urinary excretion studies, chlorothiazide appears to be incompletely absorbed from the GI tract of animals and humans (4)(5)(6). These studies reported 1658% urinary recoveries of the oral dose administered to humans.…”

Studies on drug metabolism by use of isotopes. 23. Metabolic study of 1-butyryl-4-cinnamylpiperazine in the rat during development of tolerance by using two kinds of deuterium-labeled forms

“…8 By bridging the two phenyl rings found in the azauracil substituent of 3 and 4, one may produce a variety of tricyclic azauracil substituents which could in theory exhibit all of the substituent properties detailed above. A feature common to the aryl moiety of 2-4 is the presence of a meta substituent.…”