OBJECTIVE: To review the chemistry, intracellular metabolism, pharmacokinetics, and clinical experience with didanosine (2',3'-dideoxyinosine [ddI]). DATA SOURCES: English-language articles and conference proceedings (indexing terms were didanosine, 2',3'-dideoxyinosine, and ddI). STUDY SELECTION: Available Phase I studies and abstracts determined to have clinical significance were included. DATA EXTRACTION: Clinical experience with ddI is limited to uncontrolled Phase I studies and a large "expanded-access" program. The primary outcome parameters used to evaluate ddI were the HIV surrogate markers: CD4+ lymphocytes and p24 antigen. Thus, the clinical data reviewed here must be evaluated critically and be considered preliminary until the results of studies comparing ddI with zidovudine (ZDV) and combination studies are available. DATA SYNTHESIS: Didanosine has been approved for the treatment of HIV infection in patients who are unable to tolerate ZDV because of adverse effects (e.g., anemia and neutropenia) or who experience clinical or immunologic deterioration while receiving ZDV. Compared with ZDV, ddI has a long intracellular half-life and negligible bone-marrow toxicity. It also has in vitro activity against ZDV-resistant strains of HIV. Phase I studies indicate that ddI has a beneficial effect on the CD4+ cell counts and HIV p24 antigen concentrations. As a result of the acid-labile nature of ddI, oral formulations are buffered or must be mixed with antacid to neutralize gastric pH. Bioavailability then averages 20-40 percent, depending on the dose and formulation given. The plasma half-life, total body clearance, and volume of distribution of ddI are one to two hours, 0.7-1 L/kg/h, and 0.8-1 L/kg, respectively. Painful peripheral neuropathy and pancreatitis (dose-limiting toxicities of ddI) occurred in 34 and 9 percent of patients in Phase I studies, respectively. CONCLUSIONS: Didanosine has demonstrated preliminary efficacy in the treatment of late-stage HIV infection; however, its effect on patient survival, its efficacy relative to ZDV, and its utility in combination with other agents are still under evaluation.
OBJECTIVE: To review the chemistry, intracellular metabolism, pharmacokinetics, and clinical experience with didanosine (2',3'-dideoxyinosine [ddI]). DATA SOURCES: English-language articles and conference proceedings (indexing terms were didanosine, 2',3'-dideoxyinosine, and ddI). STUDY SELECTION: Available Phase I studies and abstracts determined to have clinical significance were included. DATA EXTRACTION: Clinical experience with ddI is limited to uncontrolled Phase I studies and a large "expanded-access" program. The primary outcome parameters used to evaluate ddI were the HIV surrogate markers: CD4+ lymphocytes and p24 antigen. Thus, the clinical data reviewed here must be evaluated critically and be considered preliminary until the results of studies comparing ddI with zidovudine (ZDV) and combination studies are available. DATA SYNTHESIS: Didanosine has been approved for the treatment of HIV infection in patients who are unable to tolerate ZDV because of adverse effects (e.g., anemia and neutropenia) or who experience clinical or immunologic deterioration while receiving ZDV. Compared with ZDV, ddI has a long intracellular half-life and negligible bone-marrow toxicity. It also has in vitro activity against ZDV-resistant strains of HIV. Phase I studies indicate that ddI has a beneficial effect on the CD4+ cell counts and HIV p24 antigen concentrations. As a result of the acid-labile nature of ddI, oral formulations are buffered or must be mixed with antacid to neutralize gastric pH. Bioavailability then averages 20-40 percent, depending on the dose and formulation given. The plasma half-life, total body clearance, and volume of distribution of ddI are one to two hours, 0.7-1 L/kg/h, and 0.8-1 L/kg, respectively. Painful peripheral neuropathy and pancreatitis (dose-limiting toxicities of ddI) occurred in 34 and 9 percent of patients in Phase I studies, respectively. CONCLUSIONS:Didanosine has demonstrated preliminary efficacy in the treatment of late-stage HIV infection; however, its effect on patient survival, its efficacy relative to ZDV, and its utility in combination with other agents are still under evaluation.
Authors: P Harvie; A Désormeaux; M C Bergeron; M Tremblay; D Beauchamp; L Poulin; M G Bergeron Journal: Antimicrob Agents Chemother Date: 1996-01 Impact factor: 5.191
Authors: L Rabin; M Hincenbergs; M B Moreno; S Warren; V Linquist; R Datema; B Charpiot; J Seifert; H Kaneshima; J M McCune Journal: Antimicrob Agents Chemother Date: 1996-03 Impact factor: 5.191
Authors: G D Morse; M A Fischl; M J Shelton; M T Borin; M R Driver; M DeRemer; K Lee; C P Wajszczuk Journal: Antimicrob Agents Chemother Date: 1996-03 Impact factor: 5.191