Rifampicin liver

The co-administration of drugs which induce the metabolic enzymes in the liver or small intestine can reduce the plasma concentrations of drugs which are substrates of the enzyme, leading to reduced drug effects. For example, the plasma concentrations of many drugs which are substrates of the enzyme CYP3A4, such as cyclosporine, are decreased by coadministration of rifampicin, which is an inducer of CYP3A4. 

K., Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver, Hepatology... 

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.

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Rifampicin and other drugs that induce liver enzymes increase the metabolism of glucocorticoids (497), sufficient to reduce their therapeutic effects, for example in asthma (498). 

Bolt HM, Kappus H, Bolt M. Effect of rifampicin treatment on the metabolism of oestradiol and 17 alpha-ethi-nyloestradiol by human liver microsomes. Eur J Clin Pharmacol 1975 8(5) 301-7. 

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). 

A 56-year-old woman with liver abscesses and tuberculous lymphadenitis was given rifampicin and 2 weeks later developed a raised thyrotropin concentration of 21... 

Rifampicin-induced porphyria cutanea tarda has been described in one case, combined with altered liver function (1013). 

PXR NR1I2 603065 8856 Liver, small intestine, and colon Rifampicin, St. John s wort... 

It is known that the antibiotic rifampicin increases the amount of drug metabolizing enzyme present in the liver and consequently increases the rate of elimination of a wide range of other drugs. This experiment is designed to detect whether rifampicin affects the metabolic removal of the anti-asthma drug theophylline. Any such interaction could be of real practical importance. A marked increase in the elimination of theophylline would result in inadequate treatment of the patient s asthma. 

If rifampicin had no effect on the liver, the mean clearance in two very large groups of control and treated subjects would be virtually identical. However, with limited samples like these, both samples would probably yield imperfect estimates and their two means would almost certainly differ even in the absence of any real drug effect. 

CYP1A2 Liver Phenacetin O-deethylation (preferred1) Caffeine N3-demethylation (acceptable1) Furafylline (preferred1) Smoking 3-Methylcholanthrene Char-grilled meat Rifampicine 8-15 %... 

CYP2C8 Liver Intestine Paclitaxel 6-a-hydroxylation (preferred1) Glitazones (preferred1) Rifampicine Barbiturates 10 %... 

CYP2C9 Liver Intestine CYP2C9 2 CYP2C9 3 (S)-warfarin C6-, C7 hydroxylation (preferred1) Diclofenac 4 -hydroxylation (acceptable1) Tolbutamide para CH3-hydroxylation (acceptable1) Sulfaphenazole (preferred1) Rifampicine Phenobarbital 15-20 %... 

CYP2C18/ 2C19 Liver CYP2C19 2 CYP2C19 3 (S)-mephenytoin 4 -hydroxylation (preferred1) Ticlopidine (acceptable1, also inhibits CYP2D6) Ketoconazole Rifampicine Carbamazepine < 5%... 

The antibiotics rifamycin SV and rifampicin reduce Sulfobromophthalein (BSP) elimination in humans. Using injected oocytes, Vavricka et al. (2002) demonstrated that rifampcin is transported by OATP-C and OATP8 and that both rifampicin and rifamycin SV inhibit OATP-C, 8, -B and -A mediated BSP uptake. These results show that rifamycin SV and rifampicin interact with OATP-mediated substrate transport to different extents. Inhibition of human liver OATPs can explain the previously observed effects of rifamycin S V and rifampicin on hepatic organic anion elimination. 

A week after stopping the anti-TB drugs his liver function tests had settled and isoniazid was re-introduced at 150 mg dose, after 3 days increased to 300 mg daily. Rifampicin was then started initially at 300 mg then increased to 600 mg daily. Three weeks into the admission streptomycin was recommenced and 4 days after commencing streptomycin levels were checked and found to be trough <1 mg/L, peak 23 mg/L (target peak <40 mg/L, trough <3 mg/L). Note rifampicin can increase risk of streptomycin-induced renal dysfunction. 

Rifampicin can cause renal failure, transient disturbances of liver function tests, hyperbilirubinaemia or severe hepatotoxicity and other side-effects. Streptomycin can cause renal and ototoxicity. The combination of rifampicin and streptomycin increases the risk of streptomycin-induced renal failure. 

Wintersberger, E. Isolation of a distinct rifampicin-resistant RNA polymerase from mitochondria of yeast, neurospora and liver. Biochem. Biophys. Res. Comm. 48, 1287 (1972)... 

GGT levels may also be raised in patients taking enzyme-inducing drugs such as phenytoin or rifampicin, where levels can be commonly measured at twice ULN and potentially up to five times. Those with concomitant diseases, such as diabetes mellitus, can have GGT levels up to three times ULN, which may be due to a fatty liver. 

Drug toxicity may be more likely. A patient who becomes enzyme-induced by taking rifampicin is more likely to develop liver toxicity after paracetamol overdose by increased production of a hepatotoxic metabolite. (Such a patient will also present with a deceptively low plasma concentration of paracetamol due to accelerated metabolism, see p. 287)... 

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