Relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials Journal Article
| Authors: | Flexner, C.; van der Horst, C.; Jacobson, M. A.; Powderly, W.; Duncanson, F.; Ganes, D.; Barditch-Crovo, P. A.; Petty, B. G.; Baron, P. A.; Armstrong, D.; Bricmont, P.; Kuye, O.; Yacobi, A.; Desjardins, R.; Polsky, B. |
| Article Title: | Relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials |
| Abstract: | Two concentration-controlled trials (CCTs) defined the relationship between plasma concentrations of 3‘-deoxy-3’-fluorothymidine (alovudine) and changes in surrogate markers of antiretroviral activity. In an initial open-label CCT involving 14 subjects infected with human immunodeficiency virus (HIV), unacceptable hematologic toxicity occurred when the area under the concentration-time curve during a 12-h dosing interval (AUC12) was ���� 300 ng*h/mL. Consequently, 46 subjects were assigned to AUC12 s of 50, 100, or 200 ng*h/mL for up to 16 weeks in a prospective, randomized, double-blind CCT. Alovudine caused a concentration-dependent reduction in p24 antigen and peripheral blood mononuclear cell HIV titers within 4 weeks of start of treatment. The AUC12 producing a 50% reduction in p24 (108 ng*h/mL) had a trough concentration identical to the reported IC50 of alovudine in HIV-infected H9 cells. It may be possible to predict the antiretroviral activity of certain nucleoside analogues as a function of plasma drug concentration. © 1994 by The University of Chicago. |
| Keywords: | adult; clinical article; controlled study; aged; middle aged; human cell; clinical trial; human immunodeficiency virus infection; prospective studies; controlled clinical trial; randomized controlled trial; drug administration schedule; dose-response relationship, drug; cd4 lymphocyte count; drug blood level; double blind procedure; double-blind method; hiv infections; bone marrow toxicity; hiv; antiviral activity; antiviral agents; dideoxynucleosides; 3' fluorothymidine; humans; human; male; female; priority journal; article; hiv core protein p24 |
| Journal Title: | Journal of Infectious Diseases |
| Volume: | 170 |
| Issue: | 6 |
| ISSN: | 0022-1899 |
| Publisher: | Oxford University Press |
| Date Published: | 1994-12-01 |
| Start Page: | 1394 |
| End Page: | 1403 |
| Language: | English |
| DOI: | 10.1093/infdis/170.6.1394 |
| PROVIDER: | scopus |
| PUBMED: | 7995977 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work