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Drug Monograph on Rifampicin - page 6
Keywords: rifampicin, drug monograph, pharmacology, efficay, therapeutic uses, pharmacodynamics, Prophylaxis of meningococcal meningitis rifampin rifadin SA infections tuberculosis essay on rifampicin pharmacokinetics absorption distribution matabolism excretion bmj referecing
By Einstein10 on 30/12/2009
Level: Foundation Degree
Page Number: 6 of 11 pages: 1 2 3 4 5 6 7 8 9 10 1127 A combination of deacetylrifampicin which is still bacteriologically active and unchanged rifampicin is excreted into the bile 29.
Deacetylation of the drug favours elimination opposed to absorption 28
The unaltered rifampicin enters an enterohepatic circulation following reabsorption opposed to the 25-0-deacetyl derivative which is poorly absorbed.
Enzyme induction in the liver results in an increase in the biliary excretion of deacetylrifampicin and also increases the metabolism of rifampicin. 29
Self Induced Metabolism
Rifampicin can induce both hepatic and enterocytic metabolism by activating CYP3A4 enzyme. In a study healthy volunteers were given 450mg daily dose of Rifampicin through oral administration which led to a lower AUC and minimal blood concentration (Cmin) compared to the corresponding theoretical values with an unchanged half life. This indicated self-induced metabolism but the specific enzymes and the specific metabolism pathways have not yet been identified. 30
Excretion
Two principal pathways are employed in the excretion of rifampicin, the enterohepatic circulation (via bile)and in the urine, secondary pathway.
The elimination half life is dose dependent increasing with increasing doses. Reported half-lives of the drug initially range from 2-5 hours, but with repeated administration of the drug half life decreases as hepatic endoplasmic reticular enzymes are induced therefore serum half life decreases as does area under the curve (AUC) 31
Table 7- 28 The following table shows the effect of repeated doses on half life and AUC 32
Half-life (h) AUC (0-12h)
Day 1 3.4 131.4
Day 2 2.9 84.6
Day 6 2.5 100.5
Day 14 2.1 87.7
With repeated administration average values of half life are in the range of 2-3 hours 28
The amount of rifampicin excreted via the urinary route also increases with doses above 450mg, as a result of the biliary excretion pathway becoming saturated 8
Administration of a 900mg dose of rifampicin may result in 25% excreted via the urinary pathway 8, and amongst this 50% of the excreted drug may be in its unchanged form 31
The half-life does not differ in patients with Renal failure at doses not exceeding 900mg daily the mean half-life increased to 5-7.3 hours and 11 hours for patients with Glomerular Filtration Rates of 30-50ml/min.33
Adverse drug reactions
Condition Reaction
Cardiovascular Edema, flushing
Central nervous system Ataxia, behavioral changes, concentration impaired, confusion, dizziness, drowsiness, fatigue, fever, headache, numbness, psychosis
Dermatologic Pemphigoid reaction, pruritus, urticaria
Endocrine & metabolic Adrenal insufficiency, menstrual disorders
Hematologic Agranulocytosis, DIC, eosinophilia, hemoglobin decreased, hemolysis, hemolytic anemia, leukopenia, thrombocytopenia (especially with high-dose therapy)
Hepatic Hepatitis, jaundice
Neuromuscular & skeletal Myalgia, osteomalacia, weakness
Rena Acute renal failure, BUN increased, hemoglobinuria, hematuria, interstitial nephritis, uric acid increased
Miscellaneous Flu-like syndrome-1% to 10%: consisting of headache, fever, chills indicates
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