• YAKHAK HOEJI
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• v.39 no.6
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• pp.622-630
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• 1995

Inoculation of Friend anemia virus, which was a Kind of retro virus such as HIV, results splenomegaly, anemia, the increase of WBC counts and reverse transcriptase activity in serum. These results were due to the inhibition of the differentiation of erythroid progenitor cell by the FVA at the spleen. Using these as index of antiviral effects, we pursued the establishment of in vivo screening method for the new anti-ADS drugs. Among zidovudine, didanosine and zalcitabine, which were already approved as anti-AIDS drugs, treatment of zidovudine for 18 days in BALB/c mice inoculated with Friend anemia virus resulted the most potent inhibitory effects on the splenomegaly, the increase of WBC counts and reverse transcriptase activity, but did not recovered the anemia due to the tomcity of zidovudhie itself on the bone marrow. The antiviral effects of zidovudine was reduced in case of zidovudine treatment 7 days after Friend anemia virus inoculation. These results suggested that the sooner treatment of zidovudine would be better improved when the virus was inoculated. Human recombinant interferon itself .alpha. did not showed the antiviral activity against Friend anemia virus and did not also affected the antiviral activity of zidovudine. These results suggested that Friend anemia virus would be used as a tool in vivo screening method for the Lobster of reverse transcriptase.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.113-118
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• 2000

In order to assay the efficacy of newly synthesized antiviral compounds, pyrimidine analogs, pharmacokinetics of those were established as compared with already marketed zidovudine. Zidovudine (15, 20, 25 and 35 mg/kg), LJ142 (18.52 mg/kg) and LJ143 (15, 18.52 and 30 mg/kg) were administered orally and intravenously in rats, blood samples were collected post-injection(i.e., for 360 min) at appropriate time intervals. Those were analyzed by HPLC with UV detection at 265 nm. Pharmacokinetic parameters $(C_{max},\;T_{1/2},\;MRT,\;AUC,\;AUMC,\;Vd_{SS},\;Cl_t)$ were calculated. AUCs of zidovudine and LJ143 following I.V. dosing of $15{\sim}25\;mg/kg\;and\;15{\sim}18.18\;mg/kg$ were dose-independent. However, AUCs of zidovudine and LJ43 following I.V. dosing of $25{\sim}35\;mg/kg\;and\;18.18{\sim}30\;mg/kg$ were dose-dependent. The relative bioavailability of zidovudine, LJ142 and LJ143 following oral administration were 61.94, 46.44 and 78.24%, respectively.

• Analytical Science and Technology
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• v.36 no.6
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• pp.281-290
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• 2023

Zidovudine is an antiretroviral agent prescribed for the prevention and treatment of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). It is typically recommended to be used in combination with other antiretroviral drugs. Zidovudine has the potential to generate N-nitrosodimethylamine (NDMA) in the presence of dimethylamine and nitrite salt under acidic reaction conditions during the drug manufacturing process. NDMA is a potent human carcinogen that may be detected in drug substances or drug products. An analytical method was developed to determine NDMA in pharmaceuticals including zidovudine using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The analysis involved reversed-phase chromatography on a Kinetex F5 column with a mobile phase comprising water-acetonitrile mixtures. The detection of positively charged ions was conducted using atmospheric pressure chemical ionization (APCI). The calibration curve demonstrated excellent linearity (r = 0.9997) across the range of 1-50 ng/mL with a highly sensitive limit of detection (LOD) at 0.3 ng/mL. The developed method underwent thorough validation for specificity, linearity, accuracy, precision, robustness, and system suitability. This sensitive and specific analytical method was applied for detecting NDMA in zidovudine drug substance and its formulation currently available in the market, indicating its suitability for drug quality management purposes.

• Bulletin of the Korean Chemical Society
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• v.34 no.5
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• pp.1333-1338
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• 2013

Chitosan-based nanoparticles (CSNP) were prepared through ionic cross-linking and gelation of chitosan (CS) by tripolyphosphate (TPP). CS properties such as molecular weight, and preparation conditions were screened and the resulting nanoparticles were examined by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The obtained particles were consistently spherical with an overall diameter of approximately $107{\pm}20$ nm. They were successfully used as a carrier for Zidovudine, an anti-human immunodeficiency virus (HIV) which, to our knowledge, is novel. The encapsulation ability, loading capacity, and controlled release behavior for these CSNP was evaluated. Results indicated that their intrinsic properties were strongly affected by properties inherent to CS such as molecular weight, and by the preparation condition, such as cross-linking density, which depends on the concentration of the cross-linker. In vitro release tests for the entrapped zidovudine showed that the CNNP provided a continuous release that can last upwards 20 h.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.285-290
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• 2002

In order to assay the efficacy of newly synthesized antiviral compounds, in vitro studies of their active intracellular phosphorylated metabolites were established as compared with Zidovudine (ZDV). Antiviral base analogs require intracellular phosphorylation prior to the inhibition of HIV replication. Therefore, antiviral drugs concentrations in plasma have not reflected any direct relationship with activity or toxicity. A method has been developed to measure the concentration of total phosphorylated metabolites inside peripheral blood mononuclear cells using modified commercial radioimmunoassay (RIA). ZDV 5'-monophosphate was synthesized and used as a procedural control for RIA modification. PBMCs were isolated from whole blood and incubated with ZDV for 20 h to allow metabolic phosphorylation. Viable cells were extracted overnight with 60% methanol. After evaporation, the extract was reconstituted in Tris buffer. Samples were split into two fractions, one of which was treated with alkaline phosphatase (AP) to liberate phosphate groups. Concentrations of phosphorylated metabolites were determined by subtracting thε concentration of non-AP-treated fraction from that of the treated fraction. Recovery of phosphorylated ZDV from cell extracts was approximately 90%, and reproducibility was acceptable (coefficients of variation <15% for concentrations${\geq}$0.25 ng/mL). Intracellular concentrations $(0.135{\sim}5.019\;nmole/10^6\;cells)$ followed a nonlinear dose-response relationship over the range $0.015{\sim}2.996mM$ extracellular ZDV, with concentration-dependant saturation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.278-278
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• 1994

HIV와 유사하게 retro virus의 일종인 Friend virus of Anemia strain (FVA)을 BALB/c mice 에게 감염시 reverse transcriptase 의 활성에 의해 비장의 erythroid progenitor cell 에서 증식되므로서 비장의 비대 및 빈혈을 초래하게 된다. 이를 지표로 하여 reverse transcriptase 억제작용을 지닌 항 virus 약물을 천연성분으로 부터 검색하고자 하였다. 우선, 대조약물로 사용한 기존의 항 AIDS 약물인 zidovudine (AZT) 을 FVA 가 감염된 BAB/c mice 에게 18일간 투여시 (약 100 mg/kg/day, p.o. ) 대조군에 비해 비장의 비대 및 reverse transcriptase 활성이 90% 이상 억제되었으며, 이들의 혈청을 정상 BALB/c mice 에게 재투여시에도 유사한 결과를 나타내어 reverse transcriptase 를 억제하므로서 항 virus 작용을 나타낸다는 것을 입증하였다. 그러나, 혈액중 Hemoglobin등 빈혈의 지수는 대조군과 유사한 수치를 나타내므로서 정상으로 회복되지를 못하였다. 이것은 zidovudine 자체가 지니는 골수억제에 의한 부작용 때문인 것으로 고려된다.

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.262.1-262.1
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• 2000

• Journal of Ginseng Research
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• v.31 no.4
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• pp.175-180
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• 2007

To evaluate whether there is a relation between Korean red ginseng (KRG)-intake and the suppression of immune hyperactivation in HIV-1-infected patients, we measured serum soluble CD8 (sCD8) over 31-48 months in 168 patients. They were divided into four groups; HIV-1-infected control (n = 49), zidovudine (ZDV) group (n = 22), KRG group (n = 48), and combination of KRG and ZDV group (n = 49). In control, sCD8 and the ratio of sCD8/CD8+ T cells significantly increased by 33% (paired t-test, P < 0.05) and 54% over $21\;{\pm}\;13$ months (P < 0.001), respectively. In ZDV group, sCD8 decreased within first 6 months and then showed steady increase and the ratio also increased over $19\;{\pm}\;10$ months. In KRG group, sCD8 and the ratio of sCD/CD8+ T cells continuously decreased by 45% (P < 0.01) and 19% over $19\;{\pm}\;11$ months (P < 0.05), respectively. In combination group, sCD8 gradually decreased by 29% (P < 0.01). There was a clear difference in the changes in serum sCD8 over time among 4 groups. There was no rebound phenomenon in KRG group as shown in ZDV group. These results suggest that KRG-intake suppresses immune hyperactivation state by HIV antigen itself in the HIV-infected patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.80-80
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• 1993

(목적) 본 연구에서 사용된 바이러스는 HIV-1 nef유전자가 일부 삭제되고 대신 Chloramphenicol acetyltransferase(CAT)가 pSVCAT recombinant 바이러스다. 이러한 recombinant 바이러스를 사용하는 이유는 첫째, CAT activity가 매우 민감하므로 바이러스의 복제억제 정도를 정확하게 측정 할 수 있고 둘째, simian immunodeficiency virus(SIV)의 경우 nef 유전가 in vivo에서는 바이러스의 복제에 필수적이므로 HIV가 SIV와 유사한 것으로 미루어 본 연구에서 사용되는 recombinant SVCAT 바이러스가 안전한 것으로 고려되기 때문이다. (방법) 특히 화합물이 HIV-1의 복제에 얼마나 영향이 있는가는 1) 어느정 도의 virus inoculm을 넣었는지 2) 사용하는 cell line 3) 사용한 cell line의 infection kinetics 4) 실험의 지속기간 5) 테스트하는 assay의 sensitivity에 의존한다. 따라서 $10^{5}$ cell의 H9과 sup T1을 24 well plate에 넣고 sup T1 cell line의 경우 3일 후 항 화합물에 의한 syncytia 형성 및 CAT activity의 억제정도를 현재 AIDS drug으로 쓰이고 있는 Zidovudine을 control로 비교 관찰하였다. H9 cell line의 경우 3일 간격으로 media의 3/4을 fresh media로 바꾸어 주고 9일 후 CAT assay를 하였다. 이러한 assay에서 activity를 보이는 화합물을 reverse transcriptase와 P24 ELISA assay를 재확인하였다.다.

• The Journal of Korean Society of Virology
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• v.27 no.1
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• pp.77-86
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• 1997

To examine AZT resistance of HIV-1 isolates from AZT treated or untreated Korean, several biological characteristics such as syncytium formation, HIV-1 reverse transcriptase activity and the p24 antigen production in MT-2 cells infected with 4 HIV-1 isolates were determined. As controls, we tested HIV-1 HTLV-IIIB and pre-drug isolate as AZT susceptible strains, in addition to HIV-1 RTMC/MT-2 and post-drug isolate as AZT resistant strains. When the inoculum size of HIV-1 was 300 $TCID_{50}$/well and 100 $TCID_{50}$/well, the AZT susceptibility of AZT untreated HIV-1 isolates 8806 and 9571 were similar to that of HIV-1 HTLV-IIIB and AZT-susceptible HIV-1 strains. When we evaluated AZT resistance of isolates HIV-1 8812 and 9113 treated with AZT for 36 months by observation of syncytium formation, HIV-1 8812 showed resistance simillar to that of HIV-1 RTMC/MT-2 strain forming syncytium up to AZT $1{\mu}g/ml$, and HIV-1 9113 showed resistance identical with that of AZT-resistant HIV-1 strain which formed syncytium up to AZT $10\;{\mu}g/ml$. Especially, when we evaluated AZT resistance by HIV-1 reverse transcriptase activity and the p24 antigen production, HIV-1 isolates 8812 and 9113 showed much higher resistance (>10 - 200 fold) compared with HIV-1 RTMC/MT-2 and AZT-resistant HIV-1 strain.