The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100)

M. Tierney, J. Pottage, H. Kessler, Margaret A Fischl, D. Richman, T. Merigan, W. Powderly, S. Smith, A. Karim, J. Sherman, M. Hirsch

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an α-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients, Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV- 1 p24 levels were noted.

Original languageEnglish
Pages (from-to)549-553
Number of pages5
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume10
Issue number5
StatePublished - Dec 28 1995
Externally publishedYes

Fingerprint

Virus Diseases
Pharmacokinetics
HIV
Cataract
HIV-1
Flatulence
Maximum Tolerated Dose
Liver Function Tests
Leukopenia
CD4 Lymphocyte Count
Virus Replication
Neutropenia
Glycosylation
Toxicology
Diarrhea
Carbohydrates
Diet

Keywords

  • Antiretroviral therapy
  • Glucosidase inhibitors
  • HIV
  • N- Butyl-deoxynojirimycin
  • Pharmacokinetics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

Cite this

The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). / Tierney, M.; Pottage, J.; Kessler, H.; Fischl, Margaret A; Richman, D.; Merigan, T.; Powderly, W.; Smith, S.; Karim, A.; Sherman, J.; Hirsch, M.

In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 10, No. 5, 28.12.1995, p. 549-553.

Research output: Contribution to journalArticle

Tierney, M, Pottage, J, Kessler, H, Fischl, MA, Richman, D, Merigan, T, Powderly, W, Smith, S, Karim, A, Sherman, J & Hirsch, M 1995, 'The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100)', Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, vol. 10, no. 5, pp. 549-553.
Tierney, M. ; Pottage, J. ; Kessler, H. ; Fischl, Margaret A ; Richman, D. ; Merigan, T. ; Powderly, W. ; Smith, S. ; Karim, A. ; Sherman, J. ; Hirsch, M. / The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). In: Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 1995 ; Vol. 10, No. 5. pp. 549-553.
@article{54307e17c1304450bea8021c2ee70918,
title = "The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100)",
abstract = "Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an α-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients, Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV- 1 p24 levels were noted.",
keywords = "Antiretroviral therapy, Glucosidase inhibitors, HIV, N- Butyl-deoxynojirimycin, Pharmacokinetics",
author = "M. Tierney and J. Pottage and H. Kessler and Fischl, {Margaret A} and D. Richman and T. Merigan and W. Powderly and S. Smith and A. Karim and J. Sherman and M. Hirsch",
year = "1995",
month = "12",
day = "28",
language = "English",
volume = "10",
pages = "549--553",
journal = "Journal of acquired immune deficiency syndromes (1999)",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "5",

}

TY - JOUR

T1 - The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100)

AU - Tierney, M.

AU - Pottage, J.

AU - Kessler, H.

AU - Fischl, Margaret A

AU - Richman, D.

AU - Merigan, T.

AU - Powderly, W.

AU - Smith, S.

AU - Karim, A.

AU - Sherman, J.

AU - Hirsch, M.

PY - 1995/12/28

Y1 - 1995/12/28

N2 - Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an α-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients, Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV- 1 p24 levels were noted.

AB - Twenty-nine patients were enrolled in a phase I dose-escalating tolerance trial of N-butyl-deoxynojirimycin, an α-glucosidase I inhibitor that inhibits human immunodeficiency virus (HIV)-1 replication by altering glycosylation of gp120. Dosing was begun at 8 mg/kg/day and subsequent doses were 16, 32, 48, and 64 mg/kg/day. The maximum tolerated dose was not achieved because of slow accrual and because the study was stopped after the finding of cataracts in initial long-range rat toxicology studies. These cataracts were later shown to be transient and not found in other animals. The most common side effects were gastrointestinal, with diarrhea and flatulence occurring in most subjects, which seemed to partially improve on a modified diet that excluded complex carbohydrates. Grade III elevations in liver function tests were seen in two patients, Grade III leukopenia and neutropenia were seen in seven patients, but were only severe enough in two to require discontinuation. No significant trends in CD4 cell counts or HIV- 1 p24 levels were noted.

KW - Antiretroviral therapy

KW - Glucosidase inhibitors

KW - HIV

KW - N- Butyl-deoxynojirimycin

KW - Pharmacokinetics

UR - http://www.scopus.com/inward/record.url?scp=0028879072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028879072&partnerID=8YFLogxK

M3 - Article

C2 - 8548334

AN - SCOPUS:0028879072

VL - 10

SP - 549

EP - 553

JO - Journal of acquired immune deficiency syndromes (1999)

JF - Journal of acquired immune deficiency syndromes (1999)

SN - 1525-4135

IS - 5

ER -