rifampin and desethylamiodarone

rifampin has been researched along with desethylamiodarone* in 1 studies

Other Studies

1 other study(ies) available for rifampin and desethylamiodarone

Article	Year
Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone. Xenobiotica; the fate of foreign compounds in biological systems, 2001, Volume: 31, Issue:5 1. Amiodarone (AMI) is a potent anti-arrhythmic drug and mono-N-desethylamiodarone (MDEA) is its only known metabolite. It was found recently that in rabbit liver microsomes MDEA was biotransformed to n-3-hydroxybutyl-MDEA (3OH-MDEA). 2. In liver microsomes isolated from the untreated rabbit, the formation of 3OH-MDEA obeyed Michaelis-Menten enzyme kinetics with Km = 6.39 +/- 1.07 microM and Vmax = 0.56 +/- 0.21 nmolmin(-1) mg(-1) protein. 3. Furthermore, (1) among chemicals usually used as inhibitors of cytochrome P450, only midazolam (MDZ), cyclosporin A and ketoconazole inhibited the MDEA hydroxylase activity significantly (>60% inhibition), (2) MDZ, a substrate of CYP3A, inhibited the 30OH-MDEA formation competitively (Ki = 10 +/- 5 microM), (3) the formation rates of 3OH-MDEA correlated positively with those of 1'OH-MDZ (r = 0.81; n = 6), and (4) MDEA hydroxylase activity of microsomes isolated from rabbit rifampicin-induced cultured hepatocytes was 4-fold more active than the control. 4. Since CYP3A6 is mainly induced by rifampicin in rabbit-cultured hepatocytes, the data suggest that this isoform is involved in the biotransformation of MDEA to 3OH-MDEA. 5. Since alpha-naphthoflavone, cimetidine and quinidine also partially inhibited the MDEA hydroxylase activity, it is possible that other CYPs, such as 1A, 2C and 2D, may also be active in the metabolism of amiodarone. Topics: Amiodarone; Animals; Anti-Anxiety Agents; Anti-Arrhythmia Agents; Aryl Hydrocarbon Hydroxylases; Benzoflavones; Chromatography, High Pressure Liquid; Cimetidine; Cyclosporine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ketoconazole; Kinetics; Microsomes, Liver; Midazolam; Models, Chemical; Oxidoreductases, N-Demethylating; Protein Isoforms; Quinidine; Rabbits; Rifampin; Time Factors	2001

Article

Year

Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone.

Xenobiotica; the fate of foreign compounds in biological systems, 2001, Volume: 31, Issue:5

1. Amiodarone (AMI) is a potent anti-arrhythmic drug and mono-N-desethylamiodarone (MDEA) is its only known metabolite. It was found recently that in rabbit liver microsomes MDEA was biotransformed to n-3-hydroxybutyl-MDEA (3OH-MDEA). 2. In liver microsomes isolated from the untreated rabbit, the formation of 3OH-MDEA obeyed Michaelis-Menten enzyme kinetics with Km = 6.39 +/- 1.07 microM and Vmax = 0.56 +/- 0.21 nmolmin(-1) mg(-1) protein. 3. Furthermore, (1) among chemicals usually used as inhibitors of cytochrome P450, only midazolam (MDZ), cyclosporin A and ketoconazole inhibited the MDEA hydroxylase activity significantly (>60% inhibition), (2) MDZ, a substrate of CYP3A, inhibited the 30OH-MDEA formation competitively (Ki = 10 +/- 5 microM), (3) the formation rates of 3OH-MDEA correlated positively with those of 1'OH-MDZ (r = 0.81; n = 6), and (4) MDEA hydroxylase activity of microsomes isolated from rabbit rifampicin-induced cultured hepatocytes was 4-fold more active than the control. 4. Since CYP3A6 is mainly induced by rifampicin in rabbit-cultured hepatocytes, the data suggest that this isoform is involved in the biotransformation of MDEA to 3OH-MDEA. 5. Since alpha-naphthoflavone, cimetidine and quinidine also partially inhibited the MDEA hydroxylase activity, it is possible that other CYPs, such as 1A, 2C and 2D, may also be active in the metabolism of amiodarone.

Topics: Amiodarone; Animals; Anti-Anxiety Agents; Anti-Arrhythmia Agents; Aryl Hydrocarbon Hydroxylases; Benzoflavones; Chromatography, High Pressure Liquid; Cimetidine; Cyclosporine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ketoconazole; Kinetics; Microsomes, Liver; Midazolam; Models, Chemical; Oxidoreductases, N-Demethylating; Protein Isoforms; Quinidine; Rabbits; Rifampin; Time Factors

2001