Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers

Marc H Weiner, Eric F. Egelund, Melissa Engle, Melissa Kiser, Thomas J. Prihoda, Jonathan A Gelfond, William Mac kenzie, Charles A. Peloquin

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objectives: Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir. Methods: In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718. Results: In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC. 0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC. 0-12 or the peak concentration, but it decreased the trough concentration by 41%. Raltegravir coadministered with rifapentine was generally well tolerated. Conclusions: The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.

Original languageEnglish (US)
Article numberdkt483
Pages (from-to)1079-1085
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number4
DOIs
StatePublished - 2014

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rifapentine
Healthy Volunteers
Pharmacokinetics
Latent Tuberculosis
Raltegravir Potassium
Area Under Curve

Keywords

  • Antiretroviral therapy
  • HIV
  • Integrase strand transfer inhibitor
  • Latent tuberculosis infection
  • Rifamycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers. / Weiner, Marc H; Egelund, Eric F.; Engle, Melissa; Kiser, Melissa; Prihoda, Thomas J.; Gelfond, Jonathan A; Mac kenzie, William; Peloquin, Charles A.

In: Journal of Antimicrobial Chemotherapy, Vol. 69, No. 4, dkt483, 2014, p. 1079-1085.

Research output: Contribution to journalArticle

Weiner, MH, Egelund, EF, Engle, M, Kiser, M, Prihoda, TJ, Gelfond, JA, Mac kenzie, W & Peloquin, CA 2014, 'Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers', Journal of Antimicrobial Chemotherapy, vol. 69, no. 4, dkt483, pp. 1079-1085. https://doi.org/10.1093/jac/dkt483
Weiner, Marc H ; Egelund, Eric F. ; Engle, Melissa ; Kiser, Melissa ; Prihoda, Thomas J. ; Gelfond, Jonathan A ; Mac kenzie, William ; Peloquin, Charles A. / Pharmacokinetic interaction of rifapentine and raltegravir in healthy volunteers. In: Journal of Antimicrobial Chemotherapy. 2014 ; Vol. 69, No. 4. pp. 1079-1085.
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abstract = "Objectives: Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir. Methods: In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718. Results: In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC. 0-12) being increased by 71{\%}; the peak concentration increased by 89{\%} and the trough concentration decreased by 12{\%}. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC. 0-12 or the peak concentration, but it decreased the trough concentration by 41{\%}. Raltegravir coadministered with rifapentine was generally well tolerated. Conclusions: The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.",
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AU - Weiner, Marc H

AU - Egelund, Eric F.

AU - Engle, Melissa

AU - Kiser, Melissa

AU - Prihoda, Thomas J.

AU - Gelfond, Jonathan A

AU - Mac kenzie, William

AU - Peloquin, Charles A.

PY - 2014

Y1 - 2014

N2 - Objectives: Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir. Methods: In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718. Results: In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC. 0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC. 0-12 or the peak concentration, but it decreased the trough concentration by 41%. Raltegravir coadministered with rifapentine was generally well tolerated. Conclusions: The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.

AB - Objectives: Latent tuberculosis infection and tuberculosis disease are prevalent worldwide. However, antimycobacterial rifamycins have drug interactions with many antiretroviral drugs. We evaluated the effect of rifapentine on the pharmacokinetic properties of raltegravir. Methods: In this open-label, fixed-sequence, three-period study, 21 healthy volunteers were given: raltegravir alone (400 mg every 12 h for 4 days) on days 1-4 of Period 1; rifapentine (900 mg once weekly for 3 weeks) on days 1, 8 and 15 of Period 2 and raltegravir (400 mg every 12 h for 4 days) on days 12-15 of Period 2; and rifapentine (600 mg once daily for 10 scheduled doses) on days 1, 4-8 and 11-14 of Period 3 and raltegravir (400 mg every 12 h for 4 days) on days 11-14 of Period 3. Plasma raltegravir concentrations were measured. ClinicalTrials.gov database: NCT00809718. Results: In 16 subjects who completed the study, coadministration of raltegravir with rifapentine (900 mg once weekly; Period 2) compared with raltegravir alone resulted in the geometric mean of the raltegravir AUC from 0 to 12 h (AUC. 0-12) being increased by 71%; the peak concentration increased by 89% and the trough concentration decreased by 12%. Coadministration of raltegravir with rifapentine in Period 3 did not change the geometric mean of the raltegravir AUC. 0-12 or the peak concentration, but it decreased the trough concentration by 41%. Raltegravir coadministered with rifapentine was generally well tolerated. Conclusions: The increased raltegravir exposure observed with once-weekly rifapentine was safe and tolerable. Once-weekly rifapentine can be used with raltegravir to treat latent tuberculosis infection in patients who are infected with HIV.

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KW - Integrase strand transfer inhibitor

KW - Latent tuberculosis infection

KW - Rifamycin

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