Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs.

The safe disposal of unused opioid drugs is an area of regulatory concern. While toilet flushing is recommended for some drugs to prevent accidental exposure, there is a need for data that can support a more consistent disposal policy based on an assessment of relative risk. For drugs acting at the Mu-opioid receptor (MOR), published measurements of binding affinity (K(i)) are incomplete and inconsistent due to differences in methodology and assay system, leading to a wide range of values for the same drug thus precluding a simple and meaningful relative ranking of drug potency.

Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro: low potential for active or toxic metabolites or for drug-drug interactions.

As part of an ongoing phase 1 study, we studied the excretion of XK469 and its metabolism in patients and in vitro. Five primary metabolites were identified by HPLC/MS/MS. An oxidized product formed by cytosolic aldehyde oxidase was the predominant species both in urine and human hepatocytes in vitro.

Metabolism by N-acetyltransferase 1 in vitro and in healthy volunteers: a prototype for targeted inhibition.

Inhibition of drug metabolism is generally avoided but can be useful in limited circumstances, such as reducing the formation of toxic metabolites. Acetylation is a major pathway for drug elimination that can also convert substrates into toxic species, including carcinogens. Sulfamethoxazole, a widely used antibiotic, is metabolized via arylamine N-acetyltransferase 1.

Rifampin and rifabutin and their metabolism by human liver esterases.

1. The main metabolites of rifampin and rifabutin in man are their respective 25 deacetylated derivatives, but the enzyme(s) responsible for these biotransformations are not known. 2.