1990
DOI: 10.1056/nejm199005103221902
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Once-Daily Administration of 2′,3′-Dideoxyinosine (ddI) in Patients with the Acquired Immunodeficiency Syndrome or AIDS-Related Complex

Abstract: We conducted a Phase I open-label trial of 2',3'-dideoxyinosine (ddI) for the treatment of the acquired immunodeficiency syndrome (AIDS) and severe AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with AIDS and 17 with AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of body weight per day. Of the 17 patients previously treated with zidovudine, 13 had had hematologic side effects. The maximal … Show more

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Cited by 237 publications
(50 citation statements)
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“…The antiviral activity of AZT was -100-fold more potent than that of ddl. These findings pose a clear contrast with the currently recommended daily doses of AZT and ddl, which are both -500 mg (16)(17)(18)(19)(20), producing peak plasma concentrations of both AZT and ddl of -2-5 ,M (20,21 ) and roughly comparable antiviral activity in patients, although precise regimens for both drugs are still under study. These differences between in vitro and in vivo antiviral activity ofAZT and ddl could be due to different pharmacokinetics (e.g., intracellular half-life) ( 17,20,21 ).…”
Section: Introductioncontrasting
confidence: 49%
“…The antiviral activity of AZT was -100-fold more potent than that of ddl. These findings pose a clear contrast with the currently recommended daily doses of AZT and ddl, which are both -500 mg (16)(17)(18)(19)(20), producing peak plasma concentrations of both AZT and ddl of -2-5 ,M (20,21 ) and roughly comparable antiviral activity in patients, although precise regimens for both drugs are still under study. These differences between in vitro and in vivo antiviral activity ofAZT and ddl could be due to different pharmacokinetics (e.g., intracellular half-life) ( 17,20,21 ).…”
Section: Introductioncontrasting
confidence: 49%
“…The abundance of defective mtDNA may increase to a point at which a threshold of energy depletion may be reached and symptoms become manifested. This threshold effect on energetics in NRTI toxicity is analogous to that seen with heritable mitochondrial illnesses, including those that include mtDNA depletion Wallace, 1992a, Cooley et al, 1990Lambert et al, 1990 Distorted cristae and decreased mtDNA in CEM cells Cui et al, 1997Martin et al, 1994Medina et al, 1994Youssef and Badr, 1992 D4T Peripheral nerve Painful peripheral neuropathy in 55% of patients Browne et al, 1993Cohen et al, 1994 Distorted cristae and decreased mtDNA in CEM cells Cui et al, 1997Martin et al, 1994Medina et al, 1994 Cui et al, 1995Klecker et al, 1994Lewis et al, 1994aLewis and Tankersley, 1995Richardson et al, 1994Tennant et al, 1998 NRTIs, nucleoside reverse transcriptase inhibitors; AZT, zidovudine; DDC, zalcitabine; 3TC, lamivudine; DDI, didanosine; D4T, stavudine.…”
Section: Lewis Et Almentioning
confidence: 94%
“…Peripheral neuropathy with ddI was unexpected, based upon preclinical data . It was observed in 3% to 22% (Cooley et al, 1990;Lambert et al, 1990) of patients after 8 weeks. Peripheral neuropathy occurs in 55% of d4T-treated patients after up to 46 weeks' treatment.…”
Section: Toxicity From Other Nrtis: Varying Tissue Targetsmentioning
confidence: 99%
“…3'-azido-2' ,3'-dideoxythymidine (AZT) has been found to produce bone marrow suppression (Richman et al, 1987), 2' ,3'-dideoxyinosine (ddl) can cause pancreatitis (Cooley et al, 1990;Butler et al, 1991;Lambert et al, 1990) and both ddl and 2' ,3'-dideoxycytidine can give rise to peripheral neuropathy (Yarchoan et al, 1988;Kieburtz et al, 1992). Furthermore, prolonged treatment with these compounds is likely to promote the emergence of virus resistant to their antiviral effects.…”
Section: Introductionmentioning
confidence: 99%