• Journal of Pharmaceutical Investigation
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• 제6권3호
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• pp.58-69
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• 1976

It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

• 대한본초학회지
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• 제28권1호
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• pp.73-82
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• 2013

Objectives : Provides research basis on steaming processing method (SPM) as described in literatures 'Roegongpojaron', 'Pojadaebub', and 'Susajinam'. Methods : The following issues were considered for current investigation regarding herbal drugs: (i) categorizing SPM-applied drugs, (ii) protocols on the use of the supporting materials, (iii) kind of supporting materials, (iv) processing periods, (v) part of the herb plants, (vi) herbal efficacy, (vii) intrinsic properties and tastes of the herbal drugs, (viii) meridian tropism of the herbal drugs. Result : The number of herbal drugs was 70 species from 'Roegongpojaron', 73 from 'Pojadaebub', and 66 from 'Susajinam'. The abundance of supporting materials was in the order of alcohol, honey and tofu. The herbal parts of the roots, stem, fruit, and seed were most widely used. Based on herbal efficacy, a drug supplementing invigoration was used most, and a drug eliminating heat followed next. Based on four spirit features, herbs showing warm, cold, and mild features were used. In considering five tastes, herbs showing bitter and sweet tastes were used most. In considering meridian tropism, herbs converging to liver and kidneys were used, and drugs converging to 'Samcho, and gallbladder were not used. Conclusion : The present survey on SPM as described in 'Roegongpojaron', Pojadaebub', and 'Susajinam' indicates that there is a principal specialty on the use of supporting materials, steaming periods, steaming parts and efficacy.

• 대한통합의학회지
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• 제8권4호
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• pp.79-92
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• 2020

Purpose : The purpose of this study was to evaluate the prescription pattern of NSAIDs and GPAs in the arthritis patients over 65 years old to prevent the GI adverse events. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used agents to treat arthritis, can cause gastrointestinal (GI) adverse effects. Recent guidelines recommend that moderate risk patients who have one or two risk factors, should be prescribed either combination of non-selective NSAID (nsNSAIDs) and gastroprotective agent (GPAs) or selective NSAID alone. Methods : Study population was National Patient Sample of 2011. Number of drugs used were 138 for NSAIDs and 21 for GPAs. Chi-square test was used to compare prescribing patterns. Results : The appropriate prescription rate follows the guideline was 11.2%: co-prescription with nsNSAID and proton pump inhibitor (PPI) or misoprostol was 1.6% and selective NSAID alone was 9.6%. Inappropriate prescription rates were as follows: co-prescription with nsNSAID and Histamine-2 receptor antagonist (H2RA) or antiacid was 53.8% and nsNSAID alone was 35.0%. The appropriate prescription rate among the types of medical institute was 54.4% in tertiary hospital, 31.2% in secondary hospital, and 6.0% in primary hospital. The appropriate prescription rate among the regions was 19.4%, highest in Seoul and 4.2%, lowest in Jeju. The appropriate prescription rate among the medical departments was as follow: 12.2% in orthopaedic surgery, 11.0% in internal medicine, and 7.7% in other departments. Conclusion : This finding suggests the needs to revise the national medical insurance imbursement policy, provide continuing medical education about the guideline of medical doctors.

• Tuberculosis and Respiratory Diseases
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• 제67권4호
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• pp.325-330
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• 2009

Background: Pulmonary tuberculosis (TB) is still common disease among the elderly patients in Korea where the overall incidence of TB is decreasing. Adverse drug reactions (ADR) associated with anti-TB drugs occurs frequently. Especially the aged tends to have more frequent ADRs than younger ones. These ADRs can cause significant morbidity, compromise therapeutic effects of drugs and even induce drug resistance. Therefore we evaluated the effect of ADRs on the first-line anti-TB drugs in elderly patients with active pulmonary TB. Methods: We retrospectively reviewed the charts and radiological findings of the patients with 65 and older who were bacteriologically confirmed as active TB and treated with standard anti-TB drugs for at least 6 months. Major ADR was defined with temporary or continuous stop of any first-line drugs intake. Results: An ADR was noted in 54% of all patients. The incidence of major ADR was 32% in all elderly patients. Dermatologic ADR (9%) was the most common among the major ADRs. GI trouble (8%), arthralgia (6%), visual change (6%), hepatotoxicity (4%), and fever (1%) were also noted. The drugs responsible for major ADR were ethambutol (62%), pyrazinamide (35%), rifampin (18%) and isoniazid (9%). Major ADRs were associated with higher ESR level at the initiation of anti-TB drugs. Conclusion: First-line anti-TB drugs in elderly patients frequently caused the major ADRs. Therefore the elderly patients receiving anti-TB drugs should be closely monitored and better tolerable therapy should be considered as part of a TB research agenda.

• 대한임상독성학회지
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• 제14권2호
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• pp.100-106
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• 2016

Purpose: Beta blocker (BB) has been prescribed for anxiety and panic disorder. Patients intoxicated by psychiatric drugs have often been exposed to BB. Moreover, BB overdose has adverse effects including cardiovascular effects, which can be life-threatening. This study was conducted to identify the characteristics of BB intoxication with psychiatric drugs and the adverse effects on the cardiovascular system. Methods: A single center, retrospective study was performed from January 2010 to December 2015. A total of 4,192 patients visited the emergency department (ED) with intoxication, and 69 with BB intoxication were enrolled. Results: Overall, 64 patients (92.8%) of enrolled patients were intoxicated with drugs prescribed for the purpose of psychiatric disorders. Propranolol was the most common BB (62 cases, 96.2%), and the median dose was 140.0 mg (25%-75% 80.0-260.0). Twenty-four patients (37.5%) had experienced cardiovascular events, and these patients tended to have decreased mentality, hypotension and coingestion with quetiapine. An initial mean arterial pressure (MAP) below 65 mmHg (odds ratio 10.069, 95% confidence interval 1.572-64.481, p=0.015) was identified as a factor of cardiovascular event upon multiple logistic regression analysis. Conclusion: Initial MAP below 65 mmHg was a factor of cardiovascular adverse effect in patients of BB intoxication with psychiatric drugs.

• 대한한의학방제학회지
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• 제20권2호
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• pp.137-151
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• 2012

Objectives : provides the basis on steaming processing method (SPM) which was stated in 'Dongeuibogam' and 'Euihakipmun'. Methods : Drugs and prescriptions listed in 'Dongeuibogam' and 'Euihakipmun' were investigated by following criteria; (i) name and prescription of SPM-applied drugs, (ii) protocols on the use of the supporting materials, (iii) kind of supporting materials, (iv) processing period, (v) part of the herb plants, (vi) efficacy of herbal drugs, (vii) tastes of herbal drugs, (viii) meridian tropism of the herbal drugs. Results : 1. The number of herbs was 92 species of from 'Dongeuibogam', 87 from 'Euihakipmun', and the number of prescriptions was 197 from 'Dongeuibogam' and 119 from 'Euihakipmun'. 2. Infiltrating steaming and mixing and steaming procedures were used to process supporting materials. 3. The abundance of supporting materials was in the order of alcohol and ginger juice. 4. A twelve hour-period was most frequently used. 5. The herbal parts used most were in the order of fruit, seed, roots, and stem. 6. According to an efficacy category, a drug supplementing invigoration was used most frequently and a drug eliminating heat followed next. 7. Based on four spirit features, herbs showing warm, cold, and mild features were used most. 8. In considering five tastes, herbs showing sweet and bitter tastes were used most. 9. The herbs supporting the function of liver, kidneys, spleen, stomach, and lung were used in SPM. The herbs converging to the kidneys and the liver were conducted most in 'Dongeuibogam' and 'Euihakipmun' respectively. No case for herbal drug converging to 'Samcho' was reported. Conclusions : Our investigation on the use of SPM from 'Dongeuibogam' and 'Euihakipmun' revealed that there are special principles underlying the use of supporting materials, SPM period, parts and efficacy.

• Genomics & Informatics
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• 제6권3호
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• pp.117-125
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• 2008

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

• Genomics & Informatics
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• 제21권2호
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• pp.17.1-17.12
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• 2023

Coronavirus has left severe health impacts on the human population, globally. Still a significant number of cases are reported daily as no specific medications are available for its effective treatment. The presence of the CD147 receptor (human basigin) on the host cell facilitates the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) infection. Therefore, the drugs that efficiently alter the formation of CD147 and spike protein complex could be the right drug candidate to inhibit the replication of SARS-CoV-2. Hence, an e-Pharmacophore model was developed based on the receptor-ligand cavity of CD147 protein which was further mapped against pre-existing drugs of coronavirus disease treatment. A total of seven drugs were found to be suited as pharmacophores out of 11 drugs screened which was further docked with CD147 protein using CDOCKER of Biovia discovery studio. The active site sphere of the prepared protein was 101.44, 87.84, and 97.17 along with the radius being 15.33 and the root-mean-square deviation value obtained was 0.73 Å. The protein minimization energy was calculated to be -30,328.81547 kcal/mol. The docking results showed ritonavir as the best fit as it demonstrated a higher CDOCKER energy (-57.30) with correspond to CDOCKER interaction energy (-53.38). However, authors further suggest in vitro studies to understand the potential activity of the ritonavir.

• 분석과학
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• 제12권6호
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• pp.571-576
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• 1999

소변 시료에서 비스테로이드성 소염진통제 (Non-Steroidal Anti-Inflammatory Drugs)인 Fenamates 부류의 6종에 대해서 pentafluoropropionyl 유도체화 반응을 통하여 Gas Chromatograph/Negative Chemical Ionization-Mass Spectrometer에 감응도가 높은 유도체를 만들었다. 6종의 소염 진통제 약물에 대하여 반응성이 좋은 유도체화 반응 조건과 크로마토그래피 조건을 설정하였으며 이들 약물은 동시에 분석 가능하였고 검출한계가 4-25 pg/mL 이어서 경마 경기에서 자주 사용되고 있는 NSAIDs의 미량 성분에 대한 검출 및 법과학에서의 응용이 가능하다.

• Genomics & Informatics
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• 제19권1호
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• pp.7.1-7.13
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• 2021

Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.