• Health Policy and Management
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• v.24 no.2
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• pp.120-127
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• 2014

Background: Since December 2010, online computerized prospective drug utilization review (pDUR) has been implemented in Korea. pDUR involves the review of each prescription before the medication is dispensed to the individual patient. The pDUR is performed electronically by Health Insurance Review & Assessment Service (HIRA), which is a Korean governmental agency, and then HIRA provides medical institutions and pharmacies with information that can be helpful to them in preventing potential drug problems such as drug/drug interactions or ingredient duplication. The aim of this study was to assess the impact of the Korean pDUR implementation on the proportion of drug-drug interactions (DDIs) using claims data from HIRA. Methods: A before-after comparison of the prevalence of DDIs between prescription was conducted, using HIRA administrative claims data of medical institution from January 2010 to December 2011. The analysis unit was the prescription issued and pairs before and after. The main outcome measures were the proportion of DDIs within- (control group) or between- physician encounters. To examine the difference, a paired t-test was applied. Results: We found that DDIs proportion between prescription decreased significantly (t=3.04, p=0.0026) after the implementation of pDUR, whereas there is no significant reduction within prescription (t=1.15, p=0.2518). With respect to the prevalence of DDIs between drug groups, the most dramatic reduction was occurred between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and anti-fungal agents. Conclusion: It seems effective that giving a direct feedback to prescribers by a prospective DUR. Further research is needed to assess the impact of DUR to final outcomes such as hospitalization.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• Journal of Photoscience
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• v.11 no.1
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• pp.29-33
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• 2004

The mechanism of interaction of cyanocobalamin (CB) with bovine serum albumin (BSA) has been investigated by spectrofluorometric and circular dichroism methods. Association constant for the CB-BSA system showed that the interaction is non-covalent in nature. Binding studies in the presence of an hydrophobic probe, 8-anilino-l-naphthalene sulphonic acid, sodium salt (ANS) showed that there is hydrophobic interaction between CB and ANS and they do not share common sites in BSA. Stern-Volmer analysis of fluorescence quenching data showed that the fraction of fluorophore (protein) accessible to the quencher (CB) was close to unity indicating thereby that both tryptophan residues of BSA are involved in drug-protein interaction. The rate constant for quenching, greater than $10^{10}$ $M^{-1}$ $s^{-1}$, indicated that the drug binding site is in close proximity to tryptophan residue of BSA. Thermodynamic parameters obtained from data at different temperatures showed that the binding of CB to BSA involves hydrophobic bonds predominantly. Significant increase in concentration of free drug was observed for CB in presence of paracetamol. Circular dichroism studies revealed the change in helicity of BSA due to binding of CB to BSA.

• Archives of Pharmacal Research
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• v.14 no.4
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• pp.336-341
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• 1991

The effect of bovine serum albumin (BSA) on the encapsulation efficiency and stability of liposomes containing methotrexate (MTX) having different surface charges and cholesterol contents were investigated. The encapsulation efficiency of MTX was lower and the release of MTX was faster by the addition of BSA. The leaking of MTX from lipid bilayer depends upon the BSA concentrations. These results may be derived from the interaction of BSA with lipid bilayers. The dynamic structural changes of BSA were monitored indirectly using circular dichroism spectra. Observed dynamic structural changes of BSA with liposomes are presumed to reflect the interaction of BSA with liposomes. Negatively charged liposomes have more strong interaction with BSA than neutral and positively charged liposomes. BSA attacks lipid bilayers whether it is at the inner or at the outer phase of lipid bilayer and induces leakage of entrapped MTX. Especially, negatively charged liposomes are more sensitive than others. The inclusion of cholesterol in the lipid layers inhibits the interaction of BSA with liposomes and shows protective effect against BSA-induced leakage of MTX. To endure the attacking of BSA liposomes as drug carriers should be made using cholesterol.

• Mass Spectrometry Letters
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• v.13 no.3
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• pp.58-83
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• 2022

We developed analytical methods using high performance chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 80 unapproved compounds in dietary supplements. The target compounds for analysis were unapproved ingredients (e.g., pharmaceuticals) that have potential adverse effects on consumers owing to accidental misuse, overuse, and interaction with other medication in dietary supplement. Two analytical methods were tested to identify the optimal validation results according to AOAC guideline. As a result, limit of quantification (LOQ) was 0.14-0.5 ㎍ mL^-1; linearity (r²) was ≥ 0.99; accuracy (expressed as recovery) was 78.9-114%; precision (relative standard deviation) was ≤ 4.28% in the HPLC method. In the LC-MS/MS method, LOQ was 0.01-2 ng mL^-1, linearity (r²) was ≥0.98, accuracy was 71.7-119%; precision was ≤ 12.5%. The developed methods were applied to 51 dietary supplements collected from 2019 to 2021 through MFDS alert system. Based on our previous monitoring study, major compounds were icariin, sibutramine, yohimbine, sildenafil, tadalafil, sennosides (A, B), cascarosides (A, B, C, D), and phenolphthalein. In this study, we re-analyzed samples of detected compounds, and evaluated the statistical difference using Bland-Altman analysis to compare two analytical approaches between HPLC and LC-MS/MS. These results showed a good agreement between two methods that can be used to monitor the unapproved ingredients in dietary supplements. The developed two methods are complementarily suitable for monitoring the adulteration of 80 unapproved compounds in dietary supplements.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Journal of Integrative Natural Science
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• v.6 no.3
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• pp.138-142
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• 2013

The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of the virus into the host cells. The crucial role of the glycoprotein suggests gp120 as potential drug target for the future antiviral therapies. Identification of the binding mode of small drug like compounds has been an important goal in drug design. In the current study we attempt to propose binding mode of indole derivatives in the binding pocket of gp120. These derivatives are reported to inhibit HIV-1 by acting as attachment inhibitors that bind to gp120 and prevent the gp120-CD4 interaction and thus inhibit the infectivity of HIV-1. To elucidate the molecular basis of the small molecules interactions to inhibit the glycoprotein function we employed the molecular docking simulation approach. This study provides insights to elucidate the binding pattern of indole-based gp120 inhibitors and may help in the rational design of novel HIV-1 inhibitors with improved potency.

• Sleep Medicine and Psychophysiology
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• v.19 no.1
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• pp.18-21
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• 2012

Parasomnias induced by hypnosedatives are rare but serious side effect. Such parasomnias have not been reported with all hypnosedatives. However, frequent use of hypnosedatives, particularly nonbenzodiazepine receptor agonists is associated with parasomnias. Associated symptoms are sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping etc. Mechanisms include high affinity for $GABA_A$ receptor, interruption of the consolidation phase of memory formation by drug, pharmacokinetic or pharmacodynamic drug-drug interaction and concomitant administration with alcohol. Managements for parasomnias induced by hypnosedatives involve stopping medication, switch to other medications or nonpharmacological treatment, lowest effective dose of NBRAs (Non-Benzodiazepine Receptor Agonists), taking into consideration drug-drug interactions, identification and treatment of underlying disease states.

• Journal of Institute of Control, Robotics and Systems
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• v.10 no.6
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• pp.475-486
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• 2004

The interaction of HIV and human immune system was studied in the perspective of dynamics. We summarized the recent researches on drug scheduling using optimal control theory for HIV treatment. The drug treatment to make immune system to work properly is investigated based on mathematical models including memory CTLp. In the simulation results, it was verified that stopping medication after a certain period of treatment can lead a patient to be cured naturally by one s immune system. Also, we summarized and categorized the advantages and disadvantages of each HIV drug scheduling method. In conclusion, model-based predictive control is more efficient for making decision of drug dose than other methods, when there exist uncertainties on model parameters or state variables.

• YAKHAK HOEJI
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• v.44 no.3
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• pp.251-256
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• 2000

Sterically stabilized liposomes (SSL) composed of distearoylphosphatidylcholine, cholesterol, dicetylphosphate and distearoylphosphatiodylethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG 2000) were made by reverse phase evaporation method to prolong biological half-life and decrease toxic side effect of drug. Streptozocin (572), a water-soluble antitumor agent with short half-life, was selected as a model drug. The size of SSL was controlled by polycarbonate extrusion to 100 nm which is adequate size for long circulation in plasma. The release rate of drugs from SSL in PBS was evaluated. And the stability of STZ-containing liposomes against drug leakage into rat plasma was evaluated in order to investigate the interaction of liposome and plasma protein. Incorporation of DSPE-PEG 2000 into conventional liposomes significantly decreased the drug leakage into rat plasma.