Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis

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Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis

Stemkens, Ralf (author): Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands.

de Jager, Veronique (author): TASK, Cape Town, South Africa.

Dawson, Rodney (author): Univ Cape Town, Div Pulmonol, Cape Town, South Africa.;Univ Cape Town, Dept Med, Cape Town, South Africa.;Univ Cape Town, Lung Inst, Cape Town, South Africa.

Diacon, Andreas H. (author): TASK, Cape Town, South Africa.

Narunsky, Kim (author): Univ Cape Town, Div Pulmonol, Cape Town, South Africa.;Univ Cape Town, Dept Med, Cape Town, South Africa.;Univ Cape Town, Lung Inst, Cape Town, South Africa.

Padayachee, Sherman D. (author): Univ Cape Town, Div Pulmonol, Cape Town, South Africa.;Univ Cape Town, Dept Med, Cape Town, South Africa.;Univ Cape Town, Lung Inst, Cape Town, South Africa.

Boeree, Martin J. (author): Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, Nijmegen, Netherlands.

van Beek, Stijn W. (author): Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands

Colbers, Angela (author): Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands.

Coenen, Marieke J. H. (author): Erasmus Univ, Med Ctr, Rotterdam, Netherlands.

Svensson, Elin M., 1985- (author): Uppsala universitet,Institutionen för farmaci,Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands

Fuhr, Uwe (author): Univ Cologne, Fac Med, Ctr Pharmacol, Clin Pharmacol,Dept Pharmacol 1, Cologne, Germany.;Univ Cologne, Univ Hosp Cologne, Cologne, Germany.

Phillips, Patrick P. J. (author): Univ Calif San Francisco, UCSF Ctr TB, San Francisco, CA USA.

te Brake, Lindsey H. M. (author): Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands.

Aarnoutse, Rob E. (author): Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands.

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Radboud Univ Nijmegen, Med Ctr, Dept Pharm, Nijmegen, Netherlands TASK, Cape Town, South Africa. (creator_code:org_t)

American Society for Microbiology, 2023
2023
English.
In: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 67:10

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1–15), followed by RIF40 (days 16–30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%–115%); tolbutamide, 80% (74%–86%); omeprazole, 55% (47%–65%); dextromethorphan, 77% (68%–86%); midazolam, 62% (49%–78%), and 117% (105%–130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Keyword

tuberculosis
high-dose rifampicin
drug interactions
metabolic phenotyping

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ref (subject category)
art (subject category)

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By the author/editor: Stemkens, Ralf; de Jager, Veroni ...; Dawson, Rodney; Diacon, Andreas ...; Narunsky, Kim; Padayachee, Sher ...; show more...; Boeree, Martin J ...; van Beek, Stijn ...; Colbers, Angela; Coenen, Marieke ...; Svensson, Elin M ...; Fuhr, Uwe; Phillips, Patric ...; te Brake, Lindse ...; Aarnoutse, Rob E ...; show less...

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