Morphine glucuronidation inhibitors

Milne RW, Jensen RH, Larsen C et al. (1997) Comparison of the disposition of hepatically-generated morphine-3-glucuronide and morphine-6-glucuronide in isolated perfused liver from the guinea pig. Pharm Res 14 1014-1018 Milne RW, Larsen LA, Jorgensen KL et al. (2000) Hepatic disposition of fexofenadine influence of the transport inhibitors erythromycin and dibromosulphothalein. Pharm Resl7 1511—1515... 

Carrupt PA, Testa B, Bechalany A, El Tayar N, Descas P and Perrissoud D, Morphine-6-glucuronide and morphine-3-glucuronide as molecular chameleons with unexpected lipophilicity, /. Med. Chem., 34, 1272-1275 (1991). NB See Walther B, Carrupt PA, El Tayar N and Testa B, 8-Substituted xanthines as phosphodiesterase inhibitors Conformation-dependent lipophilicity and structure-activity relationships, Helv. Chim. Acta, 72,507-517 (1989). 

Zidovudine (AZT) is an HIV reverse transcriptase inhibitor and chain terminator that is extensively glucuronidated (70% of the dose) primarily by UGT2B7. Metabolism of AZT is induced by rifampin (PXR), ritonavir, tipranavir, and efavirenz. Zidovudine clearance is inhibited by methadone (McCance-Katz, 1998) (opiates like codeine and morphine are UGT2B7 substrates), fluconazole Trapnell, 1998, atovaquone (Lee, 1996), and valproate (Lertora, 1994). Rifampin increased the formation clearance to AZT-glucuronide by twofold (Gallicano, 1999). 

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