• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.67-73
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• 2006

Lornoxicam is a nonsteroidal anti-inflammatory drug that decreases prostaglandin synthesis by inhibiting cyclooxygenase. It has analgesic, antipyretic and antiinflammatory effects. The purpose of the present study was to evaluate the bioequivalence of two lornoxicam tablets, $Xefo^{\circledR}$ (Hyundai Pharmaceutical Ind. Co., Ltd.) and Lornocam (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of lornoxicam from the two lornoxicam formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $24.39{\pm}1.95$ years in age and $68.63{\pm}7.25$ kg in body weight, were divided into two groups and a randomized $2\;{\time}\;2$ cross-over study was employed. After a single tablet containing 4 mg as lornoxicam was orally administered, blood samples were taken at predetermined time intervals and the concentrations of lornoxicam in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t,\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Xefo^{\circledR},$ were -1.56%, 2.16% and -17.12% for $AUC_t,\;C_{max}\;and\;T_{max},$ respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log\;0.90{\sim}log\;1.05$ and $log\; 0.88{\sim}log\;1.17$ for $AUC_t\;and\;C_{max},$ respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Lornocam tablet was bioequivalent to $Xefo^{\circledR}$ tablet.

• Journal of Dental Anesthesia and Pain Medicine
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• 제23권1호
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• pp.19-28
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• 2023

Background: Fearful and anxious patients who find dental treatment intolerable without sedative and analgesic support may benefit from moderate sedation. Target controlled infusion (TCI) pumps are superior to bolus injection in maintaining low plasma and effect-site concentration variability, resulting in stable, steady-state drug concentrations. We evaluated the safety and efficacy of moderate sedation with remifentanil and propofol using TCI pumps in non-hospital dental settings. Methods: A prospective chart review was conducted on 101 patients sedated with propofol and remifentanil using TCI pumps. The charts were completed at two oral surgeons and one general dentist's office over 6 months. Hypoxia, hypotension, bradycardia, and over-sedation were considered adverse events and were collected using Tracking and Reporting Outcomes of Procedural Sedation (TROOPS). Furthermore, patient recovery time, sedation length, drug dose, and patient satisfaction questionnaires were used to measure sedation effectiveness. Results: Of the 101 reviewed sedation charts, 54 were of men, and 47 were of women. The mean age of the patients was 40.5 ±18.7 years, and their mean BMI was 25.6 ± 4.4. The patients did not experience hypoxia, bradycardia, and hypotension during the 4694 min of sedation. The average minimum Mean Arterial Pressure (MAP) and heartbeats were 75.1 mmHg and 60.4 bpm, respectively. 98% of patients agreed that the sedation technique met their needs in reducing their anxiety, and 99% agreed that they were satisfied with the sedation 24 hours later. The average sedation time was 46.9 ± 55.6 min, and the average recovery time was 12.4 ± 4.4 min. Remifentanil and propofol had mean initial effect-site concentration doses of 0.96 µ/.ml and 1.0 ng/ml respectively. The overall total amount of drug administered was significantly higher in longer sedation procedures compared to shorter ones, while the infusion rate decreased as the procedural stimulus decreased. Conclusion: According to the results of this study, no patients experienced adverse events during sedation, and all patients were kept at a moderate sedation level for a wide range of sedation times and differing procedures. The results showed that TCI pumps are safe and effective for administering propofol and remifentanil for moderate sedation in dentistry.

• Journal of Hospice and Palliative Care
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• 제19권4호
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• pp.296-302
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• 2016

목적: 호스피스 완화의료 병동에 입원한 말기 암환자가 통증을 호소할 때 진통제만 투여한 경우와 손 마사지를 병행했을 경우 통증감소의 효과를 비교한다. 방법: 단일군 시계열 설계 유사실험 연구로서 호스피스 완화의료병동에 입원한 25명의 환자를 대상으로 통증을 호소할 때 진통제를 투여하고 5분, 10분, 20분, 2시간 후에 각각 통증 점수를 측정하였고, 동일한 대상자가 다시 통증을 호소할 때, 진통제를 투여한 후 손 마사지를 병행하여 동일한 방식으로 통증점수를 측정하였다. 결과: 진통제만 투여한 군과 진통제를 투여한 후 손 마사지를 병행한 군간의 통증정도는 유의한 차이가 없었다. 그러나 두군 모두 시간이 흐름에 따라 통증정도가 유의하게 감소하였다. 결론: 손 마사지를 시행한 실험군이 대조군보다 통계적으로 유의하지는 않으나 통증정도가 낮은 경향이 있으므로 말기 암환자에게 손 마사지의 보완적 활용가치를 완전히 배제할 수는 없으며, 진통제 사용량에 따른 통증의 차이도 확인 되었으므로 간호사들은 말기 암환자를 위한 진통제 약물요법에 대하여 더 많은 교육과 연구가 요구된다.

• 대한치과마취과학회지
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• 제4권2호
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• pp.84-89
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• 2004

Background: Many studies on efficacy of preemptive analgesia have been processed in different ways. But the value of preemptive analgesia is still controversial. The goal of this study was to compare analgesic effect of an NSAID according to three different administration times for oral surgical pain. Patients and Methods: Using a randomized, parallel-group, single-center, and active-controlled test design, this study was conducted to healthy 80 patients undergoing a surgical removal of an impacted mandibular third molar requiring bone removal. The oral NSAID was first administered 1 hour preoperatively, or 1 hour postoperatively, or no scheduled administration in pre or postsurgery. Whenever patients felt at least moderate pain (score ${\ge}$ 5 on a 10-point scale) after surgery, they were instructed to take the same drug. Pain intensities and times to the first and second onset of postoperative pain from end of surgery were assessed for 24 hours. Results: Of the enrolled eighty subjects in this study, 25 patients were assigned to preemptive, 26 to post-treatment and 29 to no treatment group. The demographic distribution and duration of surgery in the three groups were statistically similar. The mean time to first onset of postoperative pain was significantly prolonged in post-treatment group (277.2 minutes, p < 0.05) compared to preemptive (158.4 minutes) and no treatment group (196.5 minutes). The mean time to second onset of postoperative pain was not significantly different among the three groups. No significant statistical difference was found among the mean pain intensities at the first and second onset of postoperative pain in the three groups. Conclusions: In this small selected group of subjects and limited study design, the analgesic effects of NSAID administered preoperatively were no longer effective for postoperative pain. The results in this population imply that scheduled postoperative analgesics before pain development are adequate for postoperative analgesia without preoperative administration.

• Toxicological Research
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• 제6권1호
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• pp.41-49
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• 1990

Aconiti Tuber is the root of Aconitum sp (Ranunclaceae) which has been considered as one of the most important medicinal plant having cordiotonic, diuretic and analgesic effect. On the other hand, it has been known that Aconiti Tuber contained toxic agent, aconitine alkaloids so that only processed Aconiti Tubers have been used as herbal drug traditionally. For the safety evaluation of processed Aconiti Tuber, quantitative determination of aconitine and acute, subacute toxicity test were performed on 5 commercial processed Aconiti Tubers. Arapid and precise method using HPLC has been developed for the separation and determination of aconitine. Samples were extracted with hydrochloric acid (pH3) and hot water decoction. In case of d-HCL extracts, the contents of aconitine were from 0.08 mg/g to trace. But in case of hot water decoction extracts, the contents of aconitine were not detected. For the investigation of Aconiti Tuber toxicity in rats, hot water decoction samples and methanol extracts were tested. 1) Acute toxicity test Hot water decoction sample and methanol extracts from Aconiti Tuber did not show any toxic effects in rats by an oral administration. $LD_50values of 2 extracts were above 10.0 g/kg. 2) Subacute toxicity study In the repeated administration study, hot water decoction samples were given orally to Sprague-Dawlay rats for 2 week at daily doses of 5.0 g/kg. The results are as follows; No toxic manifestation, body weight changes and lethality were observed during wxperimental period. There were no significant changes in serum enzyme activities such as GOT, GPT, LDH, ALP between treated and control groups. However CPK values were decreased in the Subuja-treated group. (P<0.01). In addition, no gross and microscopic changes were noted in Aconiti Tuber-treated groups.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.211-219
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• 1993

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine ($10^{-6}g/mι$), histamine ($10^{-6}g/mι$) and $BaCl_2$ ($10^{-4}g/mι$) at a concentration of $1.9{\times}10^{-4}g/mι$ in bath. But it caused a slight increase in basal tone at a concentration of $6.3{\times}10^{-4}g/mι$ and this effect was inhibited by atropine $10^{-7}g/mι.$ In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions produced by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility, But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

• The Korean Journal of Pain
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• 제21권3호
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• pp.173-178
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• 2008

Background: The intrathecal (IT) $GABA_A$ receptor antagonist, bicuculline (BIC), results in tactile allodynia (TA) through disinhibition in the spinal cord. Such disinhibition is considered to be an important mechanism for neuropathic pain. Agmatine, an endogenous polyamine, has a neuro-protective effect in the central nervous system. We investigated the analgesic effects and mechanisms of agmatine action on BIC-induced TA. Methods: Male Sprague-Dawley rats, weighting 250-300 g, were subjected to implantations of PE-10 into the lumbar subarachnoid space for IT drug injection. Five days after surgery, either $10{\mu}l$ of normal saline (NS) or agmatine ($30{\mu}g$ or $10{\mu}g$) in $10{\mu}l$ NS were injected 10 min prior to BIC ($10{\mu}g$) or NMDA ($5{\mu}g$). We assessed the degree of TA (graded 0: no response, 1: mild response, 2: moderate response, 3: strong response) every 5 min for 30 min. Areas under curves and degree of TA were expressed as mean ${\pm}$ SEM. Results were analyzed using one-way ANOVA followed by a Tukey test for multiple comparisons. P < 0.05 was considered significant. Results: IT BIC-induced strong TA reached its peak and plateaued between 10 to 15 min. IT NS-NMDA induced mild transient TA for up to 15 min. Preemptive IT AG attenuated IT BIC-induced TA dose dependently and preemptive IT AG10 completely abolished the IT NMDA-induced TA. Conclusions: Preemptive IT AG attenuated the IT BIC-induced TA through inhibitory actions on postsynaptic NMDA receptor activation. AG might be a viable therapeutic option in the treatment of neuropathic pain.

• The Korean Journal of Pain
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• 제22권3호
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• pp.199-205
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• 2009

Background: A major ingredient of green tea is epigallocatechin-3-gallate (EGCG), and this is known to have many beneficial effects for cancer prevention and also on the cardiovascular system and neurodegenerative diseases through its anti-oxidant, anti-angiogenic, anti-inflammatory, lipid-lowering and neuroprotective properties. Its actions on nociception and the spinal nervous system have been examined in only a few studies, and in these studies EGCG showed an antinociceptive effect on inflammatory and neuropathic pain, and a neuroprotective effect in motor neuron disease. This study was performed to investigate the effect of EGCG on acute thermal pain and the development of morphine tolerance at the spinal level. Methods: The experimental subjects were male Sprague-Dawley rats and the Hot-Box test was employed. A single or double-lumen intrathecal catheter was implanted at the lumbar enlargement for drug administration. An osmotic pump was used to infuse morphine for 7 days for induction of morphine tolerance. EGCG was injected repeatedly for 7 days at twice a day through the intrathecal catheter. Results: Intrathecal EGCG increased the paw withdrawal latency (PWL) after repeated administration for 7 days at twice a day, but this did not happen with administering on single bolus injection of EGCG. In addition, the antinociceptive effect of intrathecal morphine was not affected by co-administration with EGCG. A continuous 7-day infusion of morphine caused a significant decrease of the PWL in the control group (M + S, morphine plus saline). In contrast, intrathecal EGCG injection over 7 days blocked the decrease of the PWL in the experiment group (M + E, morphine plus EGCG). Conclusions: Intrathecal ECGC produced a weak antinociceptive effect for acute thermal pain, but it did not change the morphine's analgesic effect. However, the development of antinociceptive tolerance to morphine was attenuated by administering intrathecal EGCG.

• The Korean Journal of Pain
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• 제26권4호
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• pp.374-378
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• 2013

Background: Incisional pain is particularly troublesome after hysterectomy. A method called transversus abdominis plane block (TAPB) has shown promise in managing postoperative pain. In this study, we evaluated the analgesic efficacy of ultrasound-guided TAPB after hysterectomy at different time points and at each time point separately for 48 hours. Methods: Forty-two patients (ASA I, II) who were electively chosen to undergo total abdominal hysterectomy were divided into 2 groups, control (group C) and intervention (group I). Twenty-one patients underwent TAPB (group I) and 21 patients received only the standard treatment with a fentanyl pump (group C). Both groups received standard general anesthesia. For patients in group I, following the surgery and before emergence from anesthesia, 0.5 mg/kg of ropivacaine 0.2% (about 20 cc) was injected bilaterally between the internal oblique and transverse abdominis muscles using sonography. Pain scores using the Visual Analogue Scale (VAS) and drug consumption were measured at 2, 6, 12, 24, and 48 hours after TAPB. Results: There were no significant differences in demographics between the two groups. VAS scores appeared to be lower in group I, although there was no interaction with time when we compared mean VAS measurements at different time points between group I and group C (P > 0.05). The amount of fentanyl flow was consistently higher in group C, but when we compared the two groups at each time point separately, the observed difference was not statistically significant (P < 0.053). The incidence of vomiting was 10% in group I and 28% in group C. There were no complaints of itching, and sedation score was 0 to 3. There were no complications. Conclusions: This study showed that TAPB did not result in a statistically significant decrease in VAS scores at different time points. TAPB did lead to decreased fentanyl flow, but when we compared the two groups at each time point separately, the observed difference was not statistically significant.

• The Korean Journal of Pain
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• 제31권2호
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• pp.102-108
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• 2018

Background: Nefopam is a non-opioid, non-steroidal analgesic drug with fewer adverse effects than narcotic analgesics and nonsteroidal anti-inflammatory drugs, and is widely used for postoperative pain control. Because nefopam sometimes causes side effects such as nausea, vomiting, somnolence, hyperhidrosis and injection-related pain, manufacturers are advised to infuse it slowly, over a duration of 15 minutes. Nevertheless, pain at the injection site is very common. Therefore, we investigated the effect of warmed carrier fluid on nefopam injection-induced pain. Methods: A total of 48 patients were randomly selected and allocated to either a control or a warming group. Warming was performed by diluting 40 mg of nefopam in 100 ml of normal saline heated to $31-32^{\circ}C$ using two fluid warmers. The control group was administered 40 mg of nefopam dissolved in 100 ml of normal saline stored at room temperature ($21-22^{\circ}C$) through the fluid warmers, but the fluid warmers were not activated. Results: The pain intensity was lower in the warming group than in the control group (P < 0.001). The pain severity and tolerance measurements also showed statistically significant differences between groups (P < 0.001). In the analysis of vital signs before and after the injection, the mean blood pressure after the injection differed significantly between the groups (P = 0.005), but the heart rate did not. The incidence of hypertension also showed a significant difference between groups (P = 0.017). Conclusions: Use of warmed carrier fluid for nefopam injection decreased injection-induced pain compared to mildly cool carrier fluid.