• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.204-214
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• 2022

Objective: This study aimed to investigate the occurrence and types of the adverse events (AEs) associated with oral fluconazole and itraconazole and factors associated with specific types of AEs. Methods: We analyzed AEs reported by community pharmacies nationwide over 10 years using the Korea Adverse Event Reporting System database. Various AE terms were categorized into 18 types, and concomitant medications were classified by drug-drug interaction (DDI) severity. The relationship between the specific type of AE and age, sex, and number of concomitant medications was investigated using multiple logistic regression analysis. Results: A total of 879 AE reports of fluconazole and 401 reports of itraconazole were analyzed; of these reports, 321 and 83 reports of fluconazole and itraconazole, respectively, described concomitant drug administration categorized as DDI severity of contraindicated or major. Women had a higher risk of psychiatric AEs associated with fluconazole use (OR, 1.587; p=0.042). Polypharmacy increased the risk for psychiatric AEs (OR, 3.598; p<0.001 for fluconazole and OR, 2.308; p=0.046 for itraconazole). In dermatologic AEs, the mean age of patients who received itraconazole was lower than that of patients who received fluconazole (46.3±16.8 vs. 54.9±15.4; p<0.001). Co-administration of fluconazole with 1-3 drugs increased the risk of neurological AEs (OR, 1.764; p=0.028). Conclusion: When using fluconazole and itraconazole, psychiatric AEs should be noted, particularly in women and in case of polypharmacy; moreover, when fluconazole is co-administered with other drugs, attention should be paid to the occurrence of neurological AEs.

• Archives of Pharmacal Research
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• v.7 no.2
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• pp.87-93
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• 1984

The effects of ionic strength and pH on the binding of cefazolin to bovine serum albumin (BSA) were studied by UV difference spectrophotometry. As ionic strength at constant pH and temperature increases, the apparent bining constant decreased but the number of binding sites remained almost constant at 2. The constancy of the number of binding sites with increasing the ionic strength suggests that purely electrostatic forces between BSA and drug do not have great importance in the drug binding, even though there is a decrease in the apparent binding constant. Thus, the effect of ionic strength on the interaction between drug and BSA may be explained by the changes in ionic atmosphere of the aggregated BSA molecules and competitive inhibition by phosphate ions. In addition, the higher apparent binding constant at high ionic strength is explained by conformational changes of BSA from its aggregate forms into subunits. The pH effects on the afinity of interactions indicated that the binding affinity of cefazoline is higher in the neutral region than in the alkaline region. An d at high pH value, the number of binding sites decreased from 2 to 1 because of the conformational change of BSA in the alkaline region.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.545-553
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• 2021

Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

• The Korea Journal of Herbology
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• v.33 no.6
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• pp.9-18
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• 2018

Objective : Many patients take antihypertensive drugs as well as herbal medicines at the same time in order to treat other symptoms or to keep their well-being. In this study, interactions between herbal medicines and synthetic antihypertensive drugs were analyzed. Methods : To investigate the interaction between herbal medicines and synthetic antihypertensive drugs, three electronic databases, including OASIS, Mediline and Sciencedirect were searched. Experimental and clinical studies on the interaction between herbal medicines and antihypertensive drugs were independently reviewed and included. Results : Analyzing selected studies, twenty herbs were found to interact with antihypertensive drugs. Herbs found to increase the antihypertensive effect were Panax ginseng, Carthamus tinctorius, Magnolia officinalis, Silybum marianum, Scutellaria baicalensis, Schisandra chinensis, Sophora flavescens, Piper nigrum, Curcuma longa, Ginkgo biloba, Juncus effuses and Hydrastis canadensis. In contrast, Commiphora myrrha, Rhodiola rosea, Hypericum perforatum, Eurycoma longifolia, and Daturae metel were found to inhibit the antihypertensive effect. Stephania tetrandra could increase or decrease the effect depending on the type of antihypertensive drug. Epedria sínica was suspected of pharmacodynamic interaction with antihypertensive drug. Glycyrrhiza uralensis has been reported to have serious side effects in combination with antihypertensive drugs. Conclusion : These results imply that when used in combination with herbal medicines and synthetic antihypertensive drugs, proper doses and herbs which are to avoid need to be informed to the patients. Despite concerns about interactions between herbal medicines and synthetic drugs, related research is very limited. More systematic researches are needed to give information on patient safety as well as to guide clinical practice.

• Macromolecular Research
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• v.15 no.6
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• pp.547-552
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• 2007

Water soluble polymer, poly(vinyl pyrrolidone) was chosen to conjugate with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) (N-succinyl DPPE) to make a new drug delivery system. PVP with an amine group (amino-PVP) was polymerized by free radical polymerization. The amine group of amino-PVP was conjugated with the carboxylic group of N-succinyl DPPE. The resultant conjugate could form nanoparticles in the aqueous solution; these nanoparticles were termed a lipid-polymer system. The critical aggregation concentration was measured with pyrene to give a value of $1{\times}10^{-3}g/L$. The particle size of the lipid-polymer system, as measured by DLS, AFM and TEM, was about 70 nm. Lipophilic component in the inner part of the lipid-polymer system could derive the physical interaction with hydrophobic drugs. Griseofulvin was used as a model drug in this study. The loading efficiency and release profile of the drug were measured by HPLC. The loading efficiency was about 54%. The release behavior was sustained for a prolonged time of 12 days. The proposed lipid-polymer system with biodegradable and biocompatible properties has promising potential as a passive-targeting drug delivery carrier because of its small particle size.

• Archives of Pharmacal Research
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• v.12 no.3
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• pp.160-165
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• 1989

Binding of sulfaethidole to bovine serum albumin was studied by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism. Equilibrium dialysis method enabled us to estimate the total number of drug binding sites of albumin molecule. For sulfaethidole, albumin had 6 primary and 40 secondary binding sites. The primary and secondary binding constants were 0.9 * 10/sup 5/ M/sup -1/ and 0.2 * 10/sup 6/ M/sup -1/, respectivitely. 1-Anilino-8-naphthalenesulfonate (ANS) and 2-(4-hydroxylbenzeneazo)- benzoic acid (HBAB) were used as the fluorescence probe and the uv spectrophotometric probe, respectively. In fluorescence probe technique, results indicated that the number of higher affinity drug binding site of albumin was 1 and the number of lower affinity drug binding sites of albumin was 3, and the primary and secondary drug binding constants for bovine serum albumin were 2.15 * 10/sup 5/M/sup -1/ and 1.04 * 10/sup 5/ M/sup -1/, respectively. In uv difference spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above spectrophotometry, binding sites were 3 and binding constant was 1.88 * 10/sup 5/M/sup -1/. The above results suggest that several different methods should be used in ompensation for insufficient information about drug binding to albumin molecule given by only one method.

• CELLMED
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• v.2 no.2
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• pp.18.1-18.16
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• 2012

An oncology-specific database called OncoRx (http://bit.ly/cancerRx) was previously set up in cyberspace to aid clinicians in identifying interactions of anticancer drugs (ACDs) and chemotherapy regimens with traditional Chinese medicines (TCMs) and complementary and alternative medicines (CAMs). Since then, users have requested the drug-CAM interactions (DCIs) of 5 specific CAMs (cranberry, melatonin, co-enzyme Q10, huachansu, reishi mushroom) to be updated in the database. Pharmacokinetic properties (metabolism, enzyme induction/inhibition, elimination), TCM properties and DCIs of each CAM were collated with 117 ACDs using 9 hardcopy compendia and online databases as resources. Additionally, individual ACDs and CAMs were used as keywords for PubMed searches in combination with the terms 'anticancer drugs', 'drug interactions', 'herb-drug/drug-herb interactions', 'pharmacokinetic interactions' and 'pharmacodynamic interactions'. DCI parameters consisted of interaction effects, evidence summaries, proposed management plans and alternative non-interacting CAMs, together with relevant citations and update dates of the DCIs. OncoRx is also used as a case to introduce the "Four Pharmaco-cybernetic Maxims" of quality, quantity, relationship and manner to developers of digital healthcare tools. Its role in Hayne's "5S" hierarchy of research evidence is also presented. OncoRx is meant to complement existing DCI resources for clinicians and alternative medicine practitioners as an additional drug information resource that provides evidence-based DCI information for ACD-CAM interactions.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.33-37
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• 2000

One of the methods to increase the solubility of a drug is to use complexation with a cyclodextrin. Due to the hydrophobic nature of the interior cavity of the cyclodextrin, it has been known that undissociated lipophilic drugs can be included within the cyclodextrin by hydrophobic interaction. Recently, inclusion of hydrophilic or dissociated form of a drug has been investigated. In this study, the synergism of pH and complexation with $hydroxypropy-{\beta}-cyclodextrin\;(HP\;{\beta}\;CD)$ to increase the solubility of two oxicam derivatives was investigated. In addition, the effect of partition coefficient of dissociated and undissociated form of the drug on the extent of complexation with HP ${\beta}$ CD was studied. The solubility was measured by equilibrium solubility method. The solubility of tenoxicam and piroxicam increased exponentially with an increase in solution pH above the pKa of the drug in the presence and absence of HP ${\beta}$ CD. The solubility of the drugs increased linearly as a function of HP ${\beta}CD$ concentration at fixed pH. Although the stability constant of ionized species is less than that of the unionized species, the concentration of the ionized drug complex is greater than that of the unionized drug complex due to higher concentration of ionized species at pH 7.3.

• Genomics & Informatics
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• v.16 no.3
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• pp.44-51
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• 2018

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

• Mass Spectrometry Letters
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• v.8 no.4
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• pp.98-104
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• 2017

Ginseng (Panax ginseng Meyer) is a well-known health functional food used as a traditional herbal drug in Asian countries owing to its diverse pharmacological effects. Herb-drug interactions may cause unexpected side effects of co-administered drugs by the alteration of pharmacokinetics through effects on cytochrome P450 activity. In this study, we investigated the herb-drug interactions between Korean red ginseng extract (KRG) and five CYP-specific probes in mice. The pharmacokinetics of KRG extract induced-drug interactions were studied by cassette dosing of five CYP substrates for CYP1A, 2B, 2C, 2D, and 3A and the LC-MS/MS analysis of the blood concentration of metabolites of each of the five probes. The linearity, precision, and accuracy of the quantification method of the five metabolites were successfully confirmed. The plasma concentrations of five metabolites after co-administration of different doses of the KRG extract (0, 0.5, 1, and 2 g/kg) were quantified by LC-MS/MS and dose-dependent pharmacokinetic parameters were determined. The pharmacokinetic parameters of the five metabolites were not significantly altered by the dose of the KRG extract. In conclusion, the single co-administration of KRG extract up to 2 g/kg in vivo did not cause any significant herb-drug interactions linked to the modulation of CYP activity.