Einfluß von Tuberkulostatika auf die Pharmakokinetik des Digitoxins

Rifampicin, an antituberculosis drug, is usually administered for 4 to 12 months with other antituberculosis drugs or medications from other classes. A potential for drug interactions often exists because rifampicin is a potent inducer of hepatic drug metabolism, as evidenced by a proliferation of smooth endoplasmic reticulum and an increase in the cytochrome P450 content in the liver. The induction is a highly selective process and not every drug metabolised via oxidation is affected. Case reports and studies have demonstrated enhanced metabolism of several drugs; most of these interactions are clinically important. At the start of rifampicin treatment, and again at the end, clinicians must check the dosages of any accompanying medications with which rifampicin may potentially interact. Monitoring of clinical response and blood drug concentrations is essential to adjust the drug dosage during rifampicin therapy. Rifampicin also interacts with cholephils such as bilirubin and bromosulphthalein. Its pharmacokinetics are reported to be altered by ethambutol, p-aminosalicylic acid (through its excipient component), ketoconazole, cyclosporin, clofazimine, probenecid and phenobarbital through one or other of the following mechanisms--impaired absorption of rifampicin, competition between the drug and rifampicin for hepatic uptake and altered hepatic metabolism of rifampicin. Most interactions affecting rifampicin have been relatively minor or are not expected to alter its therapeutic efficacy.

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“…There are, in fact, reports describing decreases of approximately 30 to > 50% (Boman et al 1980;Peters et al 1974;Poor et al 1983).…”

Section: Digoxin and Digitoxinmentioning

confidence: 94%

Pharmacokinetic Drug Interactions with Rifampicin

Venkatesan

1992

Clinical Pharmacokinetics

123

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“…Rifampicin is also known to interfere with the effectiveness of several other drugs including anticoagulants (18,19), tolbutamids (20)(21)(22), cardiac glycosides (23) and barbiturates (21,22).…”

Section: Induction Ofhydroxylating Enzymesmentioning

confidence: 99%

Interactions between clinically used drugs and oral contraceptives.

Bolt

1994

Environ Health Perspect

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Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin). -Environ Health Perspect 102(Suppl 9): 35-38 (1994)

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“…28 The antibiotic also increases its own rate of metabolism. 11, 5 Zilly, Breimer, and Richter 37 showed that 8 days' treatment of healthy volunteers with 1,200 mg of rifampicin daily caused an almost threefold reduction of the hexobarbital half-life and a more than twofold reduction of the tolbutamide half-life, which in both cases could be attributed to an almost proportional increase in drug clearance.…”

mentioning

confidence: 99%

Influence of rifampicin on drug metabolism: Differences between hexobarbital and antipyrine

Breimer

Zilly

Richter

1977

Clin Pharma and Therapeutics

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Six healthy volunteers were treated with 1,200 mg of rifampicin daily for 8 days. Before and immediately afterward each received indocyanine green, hexobarbital, galactose, and antipyrine by intravenous infusion on 3 consecutive days. The plasma concentrations of the drugs were determined several times after infusion. The average elimination half-life of hexobarbital had decreased from 407 to 171 min and its metabolic clearance had increased almost threefold. In contrast, the average elimination half-life of antipyrine was virtually the same on both occasions (6.9 and 7.2 hr) and there was no change in metabolic clearance. In a tuberculous patient treated with rifampicin the antipyrine elimination rate was unaffected. Rifampicin did not influence indocyanine green clearance or galactose elimination capacity. Serum gamma glutamyl transferase was not affected but urinary D-glucaric acid excretion was increased during rifampicin treatment. The experiment with hexobarbital was repeated after 2 weeks in all subjects; half-lives and clearance values had returned to near control values. It appears that rifampicin is a selective inducer of oxidative drug metabolism in man.

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Einfluß von Tuberkulostatika auf die Pharmakokinetik des Digitoxins

Cited by 50 publications

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Pharmacokinetic Drug Interactions with Rifampicin

Pharmacokinetic Drug Interactions with Rifampicin

Interactions between clinically used drugs and oral contraceptives.

Influence of rifampicin on drug metabolism: Differences between hexobarbital and antipyrine

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