Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection

Debra A. Benator, Marc H Weiner, William J. Burman, Andrew A. Vernon, Zhen A. Zhao, Awal E. Khan, Brenda E. Jones, Laurie Sandman, Melissa Engle, Claudia Silva-Trigo, Poe H. Hsyu, Mark I. Becker, Charles A. Peloquin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Study Objective. To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. Design. Prospective cohort study. Setting. Three clinical research centers. Patients. Seven patients with HIV-related tuberculosis. Intervention. Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. Measurements and Main Results. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC0-21) increased 22% (geometric mean 5.01 μgasterisk inside a cirle signhr/ml [90% confidence interval (CI) 3.25-7.71] with nelfinavir vs 4.10 μgasterisk inside a cirle signhr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC0-21 for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. Conclusions. Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.

Original languageEnglish (US)
Pages (from-to)793-800
Number of pages8
JournalPharmacotherapy
Volume27
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Nelfinavir
Rifabutin
Virus Diseases
Tuberculosis
HIV
Isoniazid
Confidence Intervals
Therapeutics
Pharmacokinetics
Reverse Transcriptase Inhibitors
Drug Interactions
Nucleosides
Cohort Studies
Prospective Studies
Safety

Keywords

  • Cytochrome P450
  • Drug interactions
  • HIV
  • Human immunodeficiency virus
  • Isoniazid
  • Nelfinavir
  • Pharmacokinetics
  • Rifabutin
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection. / Benator, Debra A.; Weiner, Marc H; Burman, William J.; Vernon, Andrew A.; Zhao, Zhen A.; Khan, Awal E.; Jones, Brenda E.; Sandman, Laurie; Engle, Melissa; Silva-Trigo, Claudia; Hsyu, Poe H.; Becker, Mark I.; Peloquin, Charles A.

In: Pharmacotherapy, Vol. 27, No. 6, 06.2007, p. 793-800.

Research output: Contribution to journalArticle

Benator, DA, Weiner, MH, Burman, WJ, Vernon, AA, Zhao, ZA, Khan, AE, Jones, BE, Sandman, L, Engle, M, Silva-Trigo, C, Hsyu, PH, Becker, MI & Peloquin, CA 2007, 'Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection', Pharmacotherapy, vol. 27, no. 6, pp. 793-800. https://doi.org/10.1592/phco.27.6.793
Benator, Debra A. ; Weiner, Marc H ; Burman, William J. ; Vernon, Andrew A. ; Zhao, Zhen A. ; Khan, Awal E. ; Jones, Brenda E. ; Sandman, Laurie ; Engle, Melissa ; Silva-Trigo, Claudia ; Hsyu, Poe H. ; Becker, Mark I. ; Peloquin, Charles A. / Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection. In: Pharmacotherapy. 2007 ; Vol. 27, No. 6. pp. 793-800.
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T1 - Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection

AU - Benator, Debra A.

AU - Weiner, Marc H

AU - Burman, William J.

AU - Vernon, Andrew A.

AU - Zhao, Zhen A.

AU - Khan, Awal E.

AU - Jones, Brenda E.

AU - Sandman, Laurie

AU - Engle, Melissa

AU - Silva-Trigo, Claudia

AU - Hsyu, Poe H.

AU - Becker, Mark I.

AU - Peloquin, Charles A.

PY - 2007/6

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N2 - Study Objective. To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. Design. Prospective cohort study. Setting. Three clinical research centers. Patients. Seven patients with HIV-related tuberculosis. Intervention. Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. Measurements and Main Results. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC0-21) increased 22% (geometric mean 5.01 μgasterisk inside a cirle signhr/ml [90% confidence interval (CI) 3.25-7.71] with nelfinavir vs 4.10 μgasterisk inside a cirle signhr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC0-21 for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. Conclusions. Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.

AB - Study Objective. To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. Design. Prospective cohort study. Setting. Three clinical research centers. Patients. Seven patients with HIV-related tuberculosis. Intervention. Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. Measurements and Main Results. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC0-21) increased 22% (geometric mean 5.01 μgasterisk inside a cirle signhr/ml [90% confidence interval (CI) 3.25-7.71] with nelfinavir vs 4.10 μgasterisk inside a cirle signhr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.92]). Also, the AUC0-21 for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. Conclusions. Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.

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KW - Tuberculosis

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