Cytochrome P-450 metabolic — intermediate complex formation from p-aminobenzoic acid esters and other arylamines

1984 ◽  
Vol 9 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Zhiqiang Liu ◽  
Michael R. Franklin
Keyword(s):  
Complex Formation ◽  
Intermediate Complex ◽  
Aminobenzoic Acid ◽  
Metabolic Intermediate ◽  
Cytochrome P 450 ◽  
Acid Esters

scholarly journals Cytochrome P-450 complex formation in rat liver by the antibiotic tiamulin.

1996 ◽  
Vol 40 (1) ◽  
pp. 50-54 ◽  
Author(s):  
R F Witkamp ◽  
S M Nijmeijer ◽  
A S van Miert
Keyword(s):  
Complex Formation ◽  
Selective Inhibition ◽  
Farm Animals ◽  
Intermediate Complex ◽  
Metabolic Intermediate ◽  
Dose Dependent ◽  
Cytochrome P 450 ◽  
Related Compounds ◽  
Substrate Concentrations ◽  
Different Doses

Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds. It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex. In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 and 226 mg/kg of body weight. For comparison, another group received 300 mg of triacetyloleandomycin (TAO) per kg, which is equivalent to the 226-mg/kg tiamulin group. Subsequently, microsomal P-450 contents, P-450 enzyme activities, metabolic intermediate complex spectra, and P-450 apoprotein concentrations were assessed. In addition, effects on individual microsomal P-450 activities were studied in control microsomes at different tiamulin and substrate concentrations. In the rats treated with tiamulin, a dose-dependent complex formation as evidenced by its absorption spectrum and an increase in cytochrome P-4503A1/2 contents as assessed by Western blotting (immunoblotting) were found. The effects were comparable to those of TAO. Tiamulin induced microsomal P-450 content, testosterone 6 beta-hydroxylation rate, erythromycin N-demethylation rate, and the ethoxyresorufin O-deethylation activity. Other activities were not affected or decreased. When tiamulin was added to microsomes of control rats, the testosterone 6 beta-hydroxylation rate and the erythromycin N-demethylation were strongly inhibited. It is concluded that tiamulin is a potent and selective inducer-inhibitor of cytochrome P-450. Though not belonging to the macrolides, the compound produces an effect on P-450 similar to those of TAO and related compounds.

In-vivo kinetics of the interaction between midazolam and erythromycin in rats, taking account of metabolic intermediate complex formation

2001 ◽  
Vol 53 (5) ◽  
pp. 643-651 ◽  
Author(s):  
Sayuri Takedomi ◽  
Hirotami Matsuo ◽  
Katsuhiro Yamano ◽  
Hisakazu Ohtani ◽  
Yasufumi Sawada
Keyword(s):  
Complex Formation ◽  
Intermediate Complex ◽  
Metabolic Intermediate ◽  
In Vivo Kinetics ◽  
Kinetics Of
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