Journal article
Safety, Pharmacokinetics, and Antiviral Activity of AMD3100, a Selective CXCR4 Receptor Inhibitor, in HIV-1 Infection
Journal of acquired immune deficiency syndromes (1999), Vol.37(2), pp.1253-1262
10/01/2004
DOI: 10.1097/01.qai.0000137371.80695.ef
PMID: 15385732
Abstract
AMD3100 is a CXCR4 receptor inhibitor with anti–HIV-1 activity in vitro. We tested the safety, pharmacokinetics, and antiviral effect of AMD3100 administered for 10 days by continuous intravenous infusion in an open-label dose escalation study from 2.5 to 160 μg/kg/h. Forty HIV-infected patients with an HIV RNA level >5000 copies/mL on stable antiretroviral (ARV) regimens or off therapy were enrolled. Syncytium-inducing (SI) phenotype in an MT-2 cell assay was required in higher dose cohorts. Most subjects were black (55%), male (98%), and off ARV therapy. HIV phenotype was SI (30%), non–SI (45%), or not tested (25%). One patient (5 μg/kg/h) had serious and possibly drug-related thrombocytopenia. Two patients (40 and 160 μg/kg/h) had unexpected, although not serious, premature ventricular contractions. Most patients in the 80- and 160-μg/kg/h cohorts had paresthesias. Steady-state blood concentration and area under the concentration-time curve were dose proportional across all dose levels; the median terminal elimination half-life was 8.6 hours (range8.1–11.1 hours). Leukocytosis was observed in all patients, with an estimated maximum effect of 3.4 times baseline (95% confidence interval2.9–3.9). Only 1 patient, the patient whose virus was confirmed to use purely CXCR4 and who also received the highest dose (160 μg/kg/h), had a significant 0.9-log10 copies/mL HIV RNA drop at day 11. Overall, however, the average change in viral load across all patients was +0.03 log10 HIV RNA. Given these results, AMD3100 is not being further developed for ARV therapy, but development continues for stem cell mobilization.
Details
- Title: Subtitle
- Safety, Pharmacokinetics, and Antiviral Activity of AMD3100, a Selective CXCR4 Receptor Inhibitor, in HIV-1 Infection
- Creators
- Craig Hendrix - From the Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; †Department of Medicine and Laboratory Medicine, University of Washington School of Medicine and Harborview Medical Center, Seattle, WA; ‡Department of Medicine, Case Western Reserve University, Cleveland, OH; §Laboratory of Virology and Experimental Chemotherapy, Rega Institute for Medical Research, Leuven, Belgium; ∥Department of Internal Medicine, University of California at Davis, Davis CA; ¶AIDS Research Alliance, West Hollywood, CA; #Department of Medicine, Weill Medical College, Cornell University, New York, NY; and AnorMED, Langley, British Columbia, CanadaAnn CollierMichael LedermanDominique ScholsRichard PollardStephen BrownJ JacksonRobert CoombsMarshall GlesbyCharles FlexnerGary BridgerKarin BadelRonald MacFarlandGeoffrey HensonGary Calandra
- Resource Type
- Journal article
- Publication Details
- Journal of acquired immune deficiency syndromes (1999), Vol.37(2), pp.1253-1262
- Publisher
- Lippincott Williams & Wilkins, Inc
- DOI
- 10.1097/01.qai.0000137371.80695.ef
- PMID
- 15385732
- ISSN
- 1525-4135
- eISSN
- 1944-7884
- Language
- English
- Date published
- 10/01/2004
- Academic Unit
- Pathology; VPMA - Administration
- Record Identifier
- 9984047889602771
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