• The Journal of Korean Institute of Communications and Information Sciences
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• v.28 no.9A
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• pp.728-735
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• 2003

It is a mainly issue that provide mobility smoothly in Mobile IP networks. The IP mobility support being standardized in the IETF utilized tunneling of IP packets from a home agent to foreign agent and utilized reverse tunneling of IP packets from foreign agent to home agent. In this paper, We propose that solve the triangular routing problem in IP mobility and that lessen the messages about IETF routing optimization. Through the Mobile Routing Table on the edge router, agent process the message instead of a end node when handoff occur and that lessen the routing path length by sending directly from FA to to Correspond Node's router. This action lessen the message occurrence frequency and the packet drop. We compare the standard IP, Routing Optimization of Mobile IP, Wu's method and the proposed algorithm. Finally, the simulation results are presented.

• Molecules and Cells
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• v.45 no.12
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• pp.886-895
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• 2022

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

• Korean Journal of Veterinary Research
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• v.46 no.1
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• pp.7-12
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• 2006

We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

• YAKHAK HOEJI
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• v.45 no.4
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• pp.378-386
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• 2001

A purified histone Hl protein, p961, which plays a role in mediating the condensation of DNA into chromatin, was recently proved as an arthritis-suppressing agent in the mouse CIA model. The pharmacokinetics of p961 was carried out in rats and rabbits. The rat's blood, bile and urine samples were serially collected from the femoral vein, common bile duct, and bladder respectively, after bolus i.v. injection at low (10 mg/kg) and high (30 mg/mg) doses. The rabbit's blood samples were also collected from the marginal ear vein after bolus i.v. injection at a dose 10 mg/kg. p961 and its major metabolite in the physiological samples were analyzed by reverse-phase HPLC using a Yydac C4 protein column and a multistep water-acetonitrile gradient containing 0.24% trifluoroacetic acid. The major pharmacokinetic parameters (AUC, $C_{max}$, MRT, $t_{1}$2/, $V_{ss}$ and Cl) were estimated from the time course of plasma p961 and metabolite concentrations using WinNonlin. A two-compartment model was chosen for p961 as the most appropriate pharmacokinetic model. After i.v. injection of p961 at doses of 10 mg/kg and 30 mg/kg, more than 80% of p961 was removed rapidly from the plasma within 15 min. The plasma half-life of p961 in rats and rabbits was found not to exceed 12 min. p961 (22448.9 mol wt) was rapidly cleaved to 21612 mot wt fragment and the breakdown product appeared rapidly in the circulation with no lag phase. p961 and metabolite were not detected in rat urine and bile....

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.139-144
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• 1993

Microencapsulation of acyclovir, an effective antiviral agent which acts as a specific inhibitor of herpes DNA polymerase, by carbopol-gelatin complex coacervation has been carried out to develop an oral controlled release preparation, which could improve the absorption characteristics in GI tract. After dissolving carbopol and gelatin separately in distilled water at $40^{\circ}C$, gelatin solution was mixed with carbopol solution while stirring at the same temperature. The pH of the mixture was lowered gradually by dropwise addition of 10% HCI with continuous stirring, and then, at pH 3.5, positively charged gelatin molecules were attracted to negatively charged carbopol. These coacervation processes were observed by optical microscopy during preparation. Plasma concentrations of acyclovir in rats after an oral administration of microcapsule suspension were assayed by HPLC, and pharmacokinetic parameters were calculated based on the model-independent analyses. Two standard formulations, oral solution and intravenous bolus injection, were used as references to compare the bioavailability. It has been revealed that $C_{max}$, $T_{max}$, and MRT of microcapsule suspension were greater than those of oral solution, which results in about two-fold increases in bioavailability. Therefore, in conclusion, the carbopol-gelatin microcapsule of acyclovir might be evaluated as an effective oral controlled release preparation which could increase the bioavailability of acyclovir.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.106-110
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• 2010

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.