• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.145-153
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• 1993

Retaining a drug in the stomach by some means is sometimes necessary to extend the G1 absorption time of the drug more than 6-8 hrs. Hydrogel has often been examined for its feasibility as a dosage form, so called platform, that could be retained in the stomach due to its excellent swelling properties in the gastric fluid. In this study, polyvinylpyrrolidone (PVP) hydrogel crosslinked by albumin or acrylated albumin was synthesized in a tablet form and evaluated for its possibility as the platform. The synthesis of the hydrogel was performed by $^{60}Co\;{\gamma}-ray$ irradiation of N-vinyl-2-pyrrolidone (monomer) in the presence of a crosslinking agent: aqueous solution of albumin or acrylated albumin. Synthetic conditions such as radiation dose, dose rate and concentration of crosslinking agent were varied in order to optimize the swelling and mechanical properties of the hydrogels. Degree of swelling of albumin-crosslinked PVP (Al-PVP) was highly dependent on radiation dose, dose rate and albumin concentration: it was decreased as they increased. On the other hand, that of acrylated albumin-crosslinked PVP (Acryl-PVP) was almost independent on them except dose rate: it was decreased as the radiation dose rate increased. The compressive strength of the two hydrogels was decreased as the dose rate increased. Digestion of both PVP in artificial gastric fluid containing pepsin was delayed by the ${\gamma}-ray$ irradiation. In conclusion, Al-PVP and Acry-PVP with diverse swelling and mechanical properties could be obtained by controlling synthetic conditions, mainly the irradiation dose rate.

• Journal of Pharmaceutical Investigation
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• v.27 no.2
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• pp.109-117
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• 1997

In order to elucidate the effect of phenobarbital (PB) on the nonlinear pharmacokinetic behavior of naproxen (NAP), we compared the dose dependent hepatic intrinsic clearance, biliary excretion and protein binding of NAP in control rats to those in the PB-pretreated rats which were intraperitoneally pretreated with PB sodium (75 mg/kg) once a day for four days. NAP was injected via femoral (1.5 mg/kg) and portal(0.25, 0.5, 1.5, 15 and 30 mg/kg) vein to the control and PB-pretreated rats, respectively. And also, we measured the plasma free fraction of NAP with the equilibrium dialysis method and the biliary excreted total amounts of NAP in both rats. Plasma free fraction of NAP was decreased in lower concentration than $150\;{\mu}g/ml$ of NAP due to PB pretreatment. In higher concentration, however, plasma free fraction was increased. These in vitro results suggest that the total protein concentration was increased but the total binding capacity of NAP to protein was decreased by PB-pretreatment. The total plasma clearance and the hepatic intrinsic clearance of NAP had similar values in both groups, respectively. And, both clearances of NAP were significantly increased by PB-pretreatment. Even though the plasma free fractions of NAP in both groups were constantly remained within the concentration range according to the increase of administration dose, the hepatic intrinsic clearances of NAP were significantly increased in both groups with the increased dose. And, the biliary excreted total amounts of NAP were significantly increased by PB-pretreatment at the lower dose, but decreased at the higher dose. These in vivo results suggest that NAP represents the uncommon nonlinear pharmacokinetic behavior that the hepatic intrinsic clearance was enhanced with the increased dose, and that PB enhances further the hepatic intrinsic clearance of NAP with the increased dose due to its enzyme induction effect.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.485-493
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• 2008

The present study was carried out to elucidate the potential of, chloroform extract of Pandanus (P.) fascicularis Lamk (Family-Pandanaceae) leaves on antinociceptive, behavioral study and anti-inflammatory effects using various animal models The dried, powdered leaves of, P. fascicularis were extracted successively with petroleum ether ($60\;-\;80^{\circ}C$) and chloroform in soxhlet apparatus. The chloroform extract (yield 21.6% w/w with respected to dry powdered plant material) was selected for all experimental procedure. Two models were employed to investigate the effects on nociception, the tail immersion and hot plate method in Swiss albino mice and anti inflammatory effect were investigated by employing the carrageenan induced rat paw edema test in. adult Wister albino rats. Behavioral study was investigated by elevated plus maze method in Swiss albino mice. Results were revealed that the PFCE was found significant antinociceptive effect (P < 0.001) at the dose levels of 100, 200 and 400 mg/kg, orally in mice and produced remarkable antiinflammatory effect (P < 0.001) at the same dose levels used in the rats. Behavioral study of the PFCE has no significant anxiolysis effect when used orally. It concludes that, PFCE possessed remarkable antinociceptive effect and anti-inflammatory effect but no anxiolytic effect on animal models.

• Natural Product Sciences
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• v.9 no.2
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• pp.83-86
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• 2003

In the present study, Thespesia populnea (Malvaceae) bark was extracted with methanol and water. The extracts were vacuum dried to yield the respective methanol (MET) and aqueous extract (AET). The extracts were evaluated for hepatoprotective activity against carbon tetrachloride $(CCl_{4})$ induced liver damage at 2 dose levels (250 and 500 mg/kg). The biochemical parameters observed in serum were total bilirubin, alkaline phosphatase (ALP), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) levels and total protein. Aspartate transaminase (AST), alanine transaminase (ALT) and total protein levels in liver were also evaluated. Histopathological study on the liver tissue was also performed. The extracts exhibited dose dependent reduction in total bilirubin, ALP SGOT, SGPT, AST, ALT and increase in total protein (serum and liver) levels. The extracts also exhibited only mild hepatocytic damage compared to the $CCl_{4}$ Treated group. MET was found to exhibit higher hepatoprotection than AET.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.349-353
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• 2005

This study reports the pharmacokinetics of a novel histone deacetylase inhibitor, SD-0542, in rats after i..v. and oral administration. SD-0542 was injected intravenously at doses of 10, 20, and 40 mg/kg. The terminal elimination half-life $(t_{1/2})$, systemic clearance (Cl), and steady-state volume of distribution $(V_{ss})$ remained unaltered as a function of dose, with their values ranging from 2.0-2.5 hr, 157.2-214.1 ml/min/kg, and 11.1-17.5 L/kg, respectively, whereas, the initial serum concentration $(C_0)$ and AUC increased linearly as the dose was increased. Renal excretion of SD-0542 was minimal. Oral pharmacokinetic studies were conducted in rats at a dose of 20 mg/kg. The $T_{max}$, Cl/F, $V_{z}/F$, and $t_{1/2}$ were 2.0 hr, 92864 ml/min/kg, 16331 L/kg, and 2.0 hr, respectively. Taken together, SD-0542 showed linear pharmacokinetics over the i.v. bolus dose range studied. SD-0542 was poorly absorbed, with the absolute oral bioavailability of 0.9%.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.107-112
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• 2002

To investigate the feasibility of developing a novel melatonin plaster, the effects of vehicles and drug loading dose on the in vitro permeation of melatonin across dorsal hairless mouse skin from pressure-sensitive adhesive (PSA) matrices were examined. Vehicles employed were propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC) and diethylene glycol monoethyl ether (DGME). Among PSAs used, only $Duro-Tak^{\circledR}$ 87-2196 showed a good peeling property. The release from $Duro-Tak^{circledR}$ 87-2196 was proportional to the square root of time, and dose-dependent. The fluxes increased as the loading dose increased over the doses under solubility. The relatively high permeation flux $(3.03{\pm}1.37\;{\mu}g/cm^2/hr)$ was obtained when using PGMC at the melatonin loading dose of $45\;mg/140\;cm^2$. Lag time was not affected by the vehicles used but by the thickness spread. The melatonin plasters prepared using PGMC showed a good adhesive property onto skin, and showed no crystal formation.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.260-266
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• 2014

This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin $E_2$ in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.

• Journal of Radiation Protection and Research
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• v.40 no.1
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• pp.25-35
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• 2015

We analyzed the differential effects of histopathology, apoptosis and expression of radiation response genes after chronic low dose rate (LDR) and acute high dose rate (HDR) radiation exposure in spleen, lung and liver of rats. Female 6-week-old Sprague-Dawley rats were used. For chronic low-dose whole body irradiation, rats were maintained for 14 days in a $^{60}Co$ gamma ray irradiated room and received a cumulative dose of 2 Gy or 5 Gy. Rats in the acute whole body exposure group were exposed to an equal dose of radiation delivered as a single pulse ($^{137}Cs$-gamma). At 24 hours after exposure, spleen, lung and liver tissues were extracted for histopathologic examination, western blotting and RT-PCR analysis. 1. The spleen showed the most dramatic differential response to acute and chronic exposure, with the induction of substantial tissue damage by HDR but not by LDR radiation. Effects of LDR radiation on the lung were only apparent at the higher dose (5 Gy), but not at lower dose (2 Gy). In the liver, HDR and LDR exposure induced a similar damage response at both doses. RT-PCR analysis identified cyclin G1 as a LDR-responsive gene in the spleen of rats exposed to 2 Gy and 5 Gy gamma radiation and in the lung of animals irradiated with 5 Gy. 2. The effects of LDR radiation differed among lung, liver, and spleen tissues. The spleen showed the greatest differential effect between HDR and LDR. The response to LDR radiation may involve expression of cyclin G1.

• Journal of Pharmaceutical Investigation
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• v.34 no.4
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• pp.299-303
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• 2004

Prescription filling in powder form is performed in community pharmacy practice to adjust dose for children and patients who cannot swallow whole tablet. However, there are few reports regarding the stability of the active ingredient and possible microbial growth after the medication is dispensed to powder form. This study examined the stability of atenolol, an antihypertensive agent, and microbial growth in the unit dose pouches dispensed at twenty-one community pharmacies located in Taegu area. Randomly chosen first unit dose pouch contained 77.4% of the prescribed dose of the drug and there were only four community pharmacies that dispensed the drug within 10% deviation from the dose prescribed by physician. Surprisingly, there were three community pharmacies that dispensed the drug with greater than 40% deviation, which may pose a major concern regarding the efficacy and safety of the drug prescribed for the treatment of hypertension. Atenolol content during a month did not indicate significant change, showing 5.4%, 4.3%, and 3.3% of decrease in 50%, 80%, and 90% relative humidity conditions, respectively. Microbiological examination during a month showed less than 0.5 microorganism in high power field (hpf) in all the relative humidity conditions tested. Based on this study, pharmacy practice in community pharmacy needs to be rigorously regulated to ensure that the dose of the prescribed drug is properly incorporated into the unit dose pouch dispensed as powder form.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.261.2-261.2
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• 2002

Hypoglycemic effect of GRA was examined in multiple low dose(MLD) streptozotocin(STZ)-induced diabetic rats with regard to time of administration. Experimental methods: 20 mg/kg of STZ in 100 mM citrate buffer(pH 4.5) was injected intraperitoneally for 5 consecutive days. In co-treatment groups, GRA was administered intraperitoneally for 3 weeks at dose of 150 or 300 kg/kg. (omitted)