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The article discusses a study that proposes a single model for the decorporation of americium and plutonium through diethylene triamine pentaacetic acid (DTPA) therapy. The efficacy of the decorporation is influenced by DTPA ratio to the actinides. A higher decorporation of americium may be obtained by the affinity of the ligands to the actinide. The variation in the decorporation is influenced by the actinide, radionuclide, the dose of the DTPA and schedule of treatments.

Objective: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV., Design: : Experimental intravaginal exposure of female cynomolgus macaques to SIVmac251., Methods: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily., Results: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration., Conclusion: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency.

Objective: To determine the concentrations of intracellular active anabolites of stavudine (d4T) and didanosine (DDI) and their interpatient variability in HIV-infected patients and to explore relationships between plasma and intracellular forms., Methods: This pilot study included 28 antiretroviral-naive HIV-infected patients who received d4T (40/30 mg twice daily), ddI (400/250 mg daily) and efavirenz (600 mg daily). After 6 months of therapy, 7 ml of blood was collected between 0.5 and 16.2 h and 2.5 and 28.5 h after the last dose of d4T and ddI, respectively. Plasma samples were obtained for the determination of d4T and ddI concentrations. Peripheral blood mononuclear cells were prepared for measuring intracellular d4T and ddI triphosphates (d4T-TP and ddA-TP, respectively)., Results: d4T-TP and ddA-TP concentrations were above the limit of quantification in 25 of 26 compliant patients: median d4T-TP was 31 fmol/10(6) cells (range, 0-99) and median ddA-TP was 8 fmol/10(6) cells (range, 0-23). The half-life of d4T-TP was calculated as 7 h. Interpatient variability in d4T-TP and ddA-TP concentrations was 48% and 58%, respectively. A significant relationship was observed between plasma d4T and intracellular d4T-TP. No relation was found between ddI and ddA-TP. A linear relation was observed between the intracellular concentrations of d4T-TP and ddA-TP., Conclusion: This is the first time that data have been obtained on intracellular concentrations of d4T-TP and ddA-TP, their intracellular pharmacokinetics and interpatient variability. Other similar studies with more patients are needed to enhance knowledge of the intracellular pharmacology of the nucleoside reverse transcriptase inhibitors.