• The Korean Journal of Pain
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• v.29 no.3
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• pp.153-157
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• 2016

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the ${\mu}$-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

• Journal of Pharmaceutical Investigation
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• v.34 no.1
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• pp.43-48
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• 2004

The purpose of the present study was to evaluate the bioequivalence of two nizatidine capsules, Axid (Lilly Korea Pharm. Co., Ltd.) and Nex (Bi-nex Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The nizatidine release from the two nizatidine capsules in vitro was tested using KP Apparatus method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). The dissolution prefers of two nizatidine capsules were very similar at all dissolution media. Twenty four normal male volunteers were divided into two groups with a randomized 22 crossover study. After two capsules (300 mg nizatidine) were orally administrated, blood was taken and the concentrations of nizatidine in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were determined. The result showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two nizatidine capsules based on the Axid were -6.16%, -8.26% and -1.82%, respectively. There were no sequence effects between two capsules in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(125)(e.g., $log(0.91){\sim}log(0.97)$ and $log(0.85) {\sim}log(0.99)$ for $AUC_t$ and $C_{max}$ respectively), indicting that Nex capsule is bioequivalent to Axid capsule.

• Journal of Embryo Transfer
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• v.26 no.2
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• pp.91-96
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• 2011

The purpose of this study was to evaluate the effects of days open on subsequent reproductive performance following to estrus synchronization in the 114 lactating dairy cows. The animals were divided into two groups according to the time of estrus synchronization; viz, ${\leq}$ 85 days, and > 85 days postpartum, respectively. The estrus synchronization protocol consisted of insertion of a controlled internal drug release (CIDR) device containing 1.9 g progesterone with an injection of 250 ${\mu}g$ gonadorelin (Day 0), an injection of $PGF_2{\alpha}$ and removal of the device on Day 7, an injection of 250 ${\mu}g$ GnRH on Day 9, and TAI 17 h later. Pregnancy diagnosis was determined at 30 to 60 days after TAI using both ultrasonography and rectal palpation. The body condition score (BCS) gradually increased over the postpartum period. In estrus synchronized cows until 85 days, conception rate on first service, number of service per conception, interval from estrus synchronization to conception, and interval from calving to conception were not significantly different among two farms (P>0.05). In estrus synchronized cows after 85 days postpartum, conception rate on first service, number of service per conception and interval from calving to conception were significantly different ($P{\leq}0.05$) between herds A and B (26.8 vs 50.0%; $2.1{\pm}1.35$ vs $1.37{\pm}0.54$ times, $237.3{\pm}97.8$ vs $164.7{\pm}69.3$ days, respectively). In estrus synchronized cows after 85 days postpartum interval from estrus synchronization to conception was greater (P<0.01) in herd B than in herd A ($63.6{\pm}57.4$ vs $26.1{\pm}24.9$). These results indicate that the time of estrus synchronization for maximized the reproductive performance is before 85 days postpartum and feeding and management is important factor for high reproductive performance.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.9
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• pp.1270-1275
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• 2014

An experiment was conducted to evaluate the efficacy of porcine follicle stimulating hormone (pFSH) dosage based on body weight (BW) on ovarian responses of crossbred does. Thirty donor does were divided into 3 groups getting pFSH dosages of 3, 5, and 8 mg pFSH per kg BW, respectively, and were named as pFSH-3, pFSH-5 and pFSH-8, respectively. Estrus was synchronized by inserting a controlled internal drug release (CIDR) device and a single injection of prostaglandin $F2{\alpha}$ ($PGF2{\alpha}$). The pFSH treatments were administered twice a day through 6 decreasing dosages (25, 25, 15, 15, 10, and 10% of total pFSH amount; decreasing daily). Ovarian responses were evaluated on Day 7 after CIDR removal. After CIDR removal, estrus was observed 3 times in a day and pFSH treatments were initiated at 2 days before the CIDR removal. All does in pFSH-5 and pFSH-8 showed estrus signs while half of the does in pFSH-3 showed estrus signs. No differences (p>0.05) were observed on the corpus luteum and total ovarian stimulation among the treatment groups, while total and transferable embryos were higher (p<0.05) in pFSH-5 (7.00 and 6.71) than pFSH-3 (3.00 and 2.80) and pFSH-8 (2.00 and 1.50), respectively. In conclusion, 5 mg pFSH per kg BW dosage gave a higher number of embryos than 3 and 8 mg pFSH per kg BW dosages. The results indicated that the dosage of pFSH based on BW is an important consideration for superovulation in goats.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.191-196
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• 2001

Biodegradable polymeric microspheres were studied for their usefulness as carriers for the delivery of vaccine antigens. However, protein antigen could be denatured during microencapsulation processes due to the exposure to the organic phase and stress condition of cavitation and shear force. Therefore this study was carried out to re-evaluate the degree of protein denaturation during microencapsulation with poly(lactide-co-glycolide) (PLGA) copolymer. PLGA microspheres containing ovalbumin (OVA), prepared by W/O/W multiple emulsification method, were suspended in pH 7.4 PBS and incubated with shaking at $37.5^{\circ}C$. Drug released medium was collected periodically and analyzed for protein contents by micro-BCA protein assay. In order to evaluate the protein integrity, release medium was subjected to the analyses of SDS-PAGE and size exclusion chromatography (SEC). And enzyme-linked immunosorbent assay (ELISA) was introduced to measure the immunoreactivity of entrapped OVA and to get an insight into the three-dimensional structure of epitope. The structures of entrapped protein were not affected significantly by the results of SDS-PAGE and SEC. However, immunoreactivity of released antigen was varied, revealing the possibility of protein denaturation in some microspheres when it was evaluate by ELISA method. Therefore, in order to express the degree of protein denaturation, antigenicity ratio (AR) was obtained as follows: amount of immunoreactivity of OVA/total amount of OVA released ${\times}100(%)$. ELISA method was an efficient tool to detect a protein denaturation during microencapsulation and the comparison of AR values resulted in more accurate evaluation for immunoreactivity of entrapped protein.

• Reproductive and Developmental Biology
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• v.37 no.1
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• pp.29-33
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• 2013

The objective of this work was to analyze the concentrations of progesterone (P4) and estrogen (E2) hormones changed during estrus synchronization in dairy heifers. Estrus synchronization was carried out with CIDR$^{(R)}$ (Controlled Intravaginal Drug Release) devices. Corpus luteum (CL) was classified into three grades based on its size and palpable characteristics. The concentrations of P4 and E2 were measured by enzyme-amplified chemiluminescence. Serum P4 concentration was markedly low at the estrus stage (36 hrs after removal of CIDR) compared to other stages, while E2 concentration was kept high during estrus stage. The serum P4 concentration was highest in the CL classified into grade I. These results indicate that P4 concentration could be used as a criteria for determining recipients for artificial insemination or embryo transfer in dairy cattle.

• Journal of Microbiology and Biotechnology
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• v.20 no.2
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• pp.433-437
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• 2010

In the course of screening for novel modulators of cell cycle progression and apoptosis as anticancer drug candidates, we generated an analog of sangivamycin, MCS-C2, which was elucidated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. In the present study, we evaluated the molecular mechanisms of MCSC2-induced cell cycle arrest and apoptosis in A549 human lung cancer cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured the DNA content of A549 cells treated with $5\;{\mu}M$ MCS-C2 using flow cytometry. The analysis revealed an appreciable $G_2$ phase arrest in treated cells. This event was associated with significant upregulation of p53 and $p21^{Cip1}$. In addition, the TUNEL assay was used to examine apoptotic induction in treated cells, and the effects of MCS-C2 on the expression of apoptosis-associated proteins were examined by Western blot. Apoptotic induction in MCS-C2-treated A549 cells was associated with cytochrome c release from mitochondria, which in turn resulted in the activation of caspase-9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Based on these results, we conclude that MCS-C2 is a candidate therapeutic agent for the treatment of human lung cancer via upregulation and activation of p53.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.120-126
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• 2005

The objective of this study was to investigate the effects of sodium lauryl sulfate upon the saturation solubility of carbamazepine, its dissolution kinetics, and $T_{50\%}$ defined as the time required for dissolving $50\%$ of carbamazepine. Water, 0.1N-HCI, and phosphate buffers at pH 4.0 and 6.8 containing 0.1, 0.5, 1, and $2\%$ sodium lauryl sulfate were used as dissolution media. The dissolution study was conducted by using the USP dissolution apparatus II with an agitation rate of 75 rpm. Samples of the dissolution media were taken in 7, 15, 30, 45, 60, 75, and 90 min, and the amounts of carbamazepine were determined spectrophotometrically at 285 nm. All dissolution data were fitted well into a four-parameter exponential equation: $Q\;=\;a(1\;-\;e^{-bxt})\;+\;c(1\;-\;e^{-dxt})$. In this equation Q represented $\%$ carbamazepine dissolved at a time t, and a, b, c, and d were constants. This equation led to the calculation of dissolution rates at various time points and $T_{50\%}$. It was found that the dissolution rate of carbamazepine was directly proportional to the aqueous concentration of sodium lauryl sulfate. In addition, under our experimental conditions $T_{50%}$ values ranged from 37.8 to 4.9 min. It was interesting to note that $T_{50\%}$ declined rapidly as the surfactant concentration increased from 0.1 to $0.5\%$, whereas it declined more slowly at concentrations greater than $1\%$. These results clearly demonstrated that the dissolution rate of carbamazepine and duration of its dissolution test could be tailored by optimizing the amount of sodium lauryl sulfate in a dissolution medium.

• Journal of Periodontal and Implant Science
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• v.26 no.1
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• pp.317-333
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• 1996

The main goal of periodontal regeneration is to be achieved by epithelial exclusion, periodontal ligament cell activation or alveolar bone regeneration. The purpose of this study was to investigate on the physico- chemical and biological characteristics of biodegradable chitosan beads. Chitosan beads were fabricated by ionic gelation with sodium tripolyphosphate and they had the size in 300um diameter. As therapeutic agent, flurbiprofen was incorporated into the beads by 10, 20% loading contents. The release of drugs from the chitosan beads was measured in vitro. Also, biological activity tests of flurbiprofen loaded chitosan beads including cytotoxicity test, ihhibition of $IL-1{\beta}$ production, suppression to $PGE_2$ production, collagenase inhibition test, the ability of total protein synthesis, and tissue response were evaluated. The amount of flurbiprofen released from chitosan was 33-50% during 7 days. Minimal cytotoxicity was observed in chitosan beads. Flurbiprofen released from chitosan beads significantly suppressed the $IL-1{\beta}$ production of monocyte, $PGE_2$ production and markedly inhibited collagenase activity. Meanwhile, flurbiprofen released from this system showed increased ability for protein synthesis. Throughout 4 -week implantation period, no significant inflammatory cell infiltrated around chitosan bead and also fibroblast like cell types at the beads - tissue interface were revealed with gradual degradation of implanted chitosan beads. From these results, it was suggested that flurbiprofen loaded chitosan beads can be effectively useful for biocompatible local delivery system in periodontal regeneration.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6301-6306
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• 2014

Cervical cancer is one the most common malignancies among females. In recent years, its incidence rate has shown a rising trend in some countries so that development of anticancer drugs for cervical cancer is an urgent priority. In our recent anticancer drug discovery screen, 1, 2-di (quinazolin-4-yl)diselane (LG003) was found to possess wide spectrum anticancer efficacy. In the present work, the in vitro anticancer activity of LG003 was evaluated in the SiHa cervical cancer cell line. Compared with commercial anticancer drugs 10-hydroxycamptothecin, epirubicin hydrochloride, taxol and oxaliplatin, LG003 showed better anticancer activity. Furthermore, inhibition effects were time- and dose-dependent. Morphological observation exhibited LG003 treatment results in apoptosis like shrinking and blebbing, and cell membrane damage. Lactate dehydrogenase release assay revealed that LG003 exerts such effects in SiHa cells through a physiology pathway rather than cytotoxicity, which suggests that title compound LG003 can be a potential candidate agent for cervical cancer.