Analysis of in vivo absorption of didanosine tablets in male adult dogs by HPLC

Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 1C. For an isocratic run, the fiux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 mL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at 20 1C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration,aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile.Chitosan microspheres were produced under fiuidized bed,followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm.The pellets were then coated with Kollidon VA64 and Kollicoat MAE100P in water dispersion to depict a sustained release profile.Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine.Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine.

Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study

AIM To identify significant liver disease [including nodular regenerative hyperplasia(NRH)] in asymptomatic Didanosine(DDI) exposed human immunodeficiency virus(HIV) positive patients.METHODS Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography(TE). Those with alanine transaminase(ALT) above upper limit normal and/or TE > 7.65 k Pa underwent ultrasound scan(U/S). Patients with:(1) abnormal U/S; or(2) elevated ALT plus TE > 7.65 k Pa;or(3) TE > 9.4 k Pa were offered trans-jugular liver biopsy(TJLB) with hepatic venous pressure gradient(HVPG) assessment.RESULTS Ninety-nine patients were recruited, median age 50 years(range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years(range 0.5-14.6). Eighty-one had a valid TE readings(interquartile range/score ratio < 0.3): 71(88%) < 7.65 k Pa, 6(7%) 7.65-9.4 k Pa and 4(6%) > 9.4 k Pa. Seventeen(17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mm Hg. Commonest histological findings were steatosis(n = 6), normal architecture(n = 4) and NRH(n = 2), giving a prevalence of previously undiagnosed NRH of 2%(95%CI: 0.55%, 7.0%).CONCLUSION A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.

A one-year clinical trial using didanosine, stavudine and nevirapine for highly active antiretroviral therapy

Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.