Induction rifampicin

Rifampicin is a potent liver-enzyme inducer that inereases the metabolism and loss of extensively metabolised beta blockers sueh as propranolol and metoproioi. Rifampicin may also interact by mechanisms other than enzyme induction. Rifampicin increases duodenal P-glyeoprotein expres-... 

By using in vitro preparations of human enzymes it is possible to predict those antibiotics that will adversely affect the metabolism of other drugs [110]. Such studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/ml, did not inhibit human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 [34], In an in vitro hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4) [34], an isoenzyme which rifampicin is known to induce [109],... 

Figure 13.2 Schematic representation of the creation of hPXR humanized mice. The humanization was achieved in the liver only when the liver-specific albumin promoter was used to direct the transgene expression, or in both the liver and the intestine when the fatty acid binding protein promoter was used. PCN, pregnenolone-16a-carbonitrile RIF, rifampicin. + and mean induction and lack of induction, respectively.

Of all N Rs involved in xenobiotics metabolism induction, PX R is the most prominent one. PXR functions as a xenobiotic sensor and is activated by a large variety of chemically diverse compounds, for example lovastatin, nifedipine, rifampicin, SR12813, troglitazone or hyperforin (Chart 14.3), many of them standard therapeutic agents for common diseases [20-25]. 

Rifampicin CYP inducer Pre-treatment of rats with Rifampicin for up to 2 weeks pre-experiment can be used to assess the effect of induction of intestinal metabolism on Peg values [135]... 

Chen Y, Ferguson SS, Negishi M, Goldstein JA. Induction of human CYP2C9 by rifampicin, h5 perforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther 2004 308(2) 495-501. 

Fromm MF, Dilger K, Busse D, Kroemer HK, Eichelbaum M, Klotz U. Gut wall metabolism of verapamil in older people effects of rifampicin-mediated enzyme induction. Br J Clin Pharmacol 1998 45(3) 247-255. 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

Reduced efficacy of gliclazide has been attributed to induction of CYP2C9 by rifampicin (182). 

Rifampicin greatly reduced the plasma concentrations of simvastatin and simvastatin acid in 10 healthy volunteers in a randomized, crossover study (57). Because the half-life of simvastatin was not affected by rifampicin, induction of CYP3A4-mediated first-pass metabolism of simvastatin in the intestine and liver probably explains this interaction. 

In patients taking glucocorticoids for Addison s disease, rifampicin may necessitate an increase in glucocorticoid dosage. Thus, incipient adrenal insufficiency can be unmasked by rifampicin (SEDA-13, 261). The phenomenon is due to liver enzyme induction (1008). 

The combination of rifampicin and isoniazid reduces serum concentrations of 25-hydroxy cholecalciferol. Rifampicin acts by induction of an enzyme that promotes conversion of 25-hydroxycholecalciferol to an inactive metabolite, and isoniazid acts by inhibiting 25-hydroxyla-tion and 1-hydroxylation (SEDA-14, 258). Children or pregnant women with tuberculosis have increased calcium requirements independent of rifampicin administration... 

Benzodiazepines + smoking, rifampicin —> due to enzyme induction, plasma concentration of the benzodiazepine is reduced. 

Gashaw I, Kirchheiner J, Goldammer M, Bauer S, Seidemann J, Zoller K, Mrozikiewicz PM, Roots I, Brockmoller J. Cytochrome p450 3A4 messenger ribonucleic acid induction by rifampicin in human peripheral blood mononuclear cells correlation with alprazolam pharmacokinetics. Clin Pharmacol Ther 2003 74 448-457. 

Gallicano KD, Sahai J, Shukla VK, et al. Induction of ZDV glucuronidation and animation pathways by rifampicin in HIV-infected patients. Br J Clin Pharmacol 1999 48(2) 168-179. 

---