• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.335-342
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• 2018

The incidence and mortality of various cancers are associated with sex-specific disparities. Sex differences in cancer epidemiology are one of the most significant findings. Men are more prone to die from cancer, particularly hematological malignancies. Sex difference in cancer incidence is attributed to regulation at the genetic/molecular level and sex hormones such as estrogen. At the genetic/molecular level, gene polymorphism and altered enzymes involving drug metabolism generate differences in cancer incidence between men and women. Sex hormones modulate gene expression in various cancers. Genetic or hormonal differences between men and women determine the effect of chemotherapy. Until today, animal studies and clinical trials investigating chemotherapy showed sex imbalance. Chemotherapy has been used without consideration of sex differences, resulting in disparity of efficacy and toxicity between sexes. Based on accumulating evidence supporting sex differences in chemotherapy, all clinical trials in cancer must incorporate sex differences for a better understanding of biological differences between men and women. In the present review, we summarized the sex differences in (1) incidence and mortality of cancer, (2) genetic and molecular basis of cancer, (3) sex hormones in cancer incidence, and (4) efficacy and toxicity of chemotherapy. This review provides useful information for sex-based chemotherapy and development of personalized therapeutic strategies against cancer.

• Journal of Pharmaceutical Investigation
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• v.9 no.3
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• pp.1-8
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• 1979

The main route of metabolism of isonicotinic acid hydrazid (INH) in man is its conjugation with acetyl coenzyme A to form acetyl-INH. The reaction is catalyzed by an N-acetyl transferase in the liver. The acetylated drug can be excreted by the kidney more efficiently than INH, and the biological half-life of the drug in the body depends upon how rapidly the drug can be acetylated. This report measured the concentration of INH in the blood of 147 individuals 6 hours after they received a standard dose (9.8mg/kg) and plotted the data as a frequeney distribution hiotogram. There was bimodality, with a mean for one subpopulation at approximately $0.6{\sim}0.8\;mcg/ml.$, and a mean for the other subpopulation between 2.8 and 4.0mcg/ml. As might be expected slow acetylators of INH are more likely to develop a cumulative toxicity to the drug. The principle ,toxicity to INH is a peripheral neuritis but this adverse effect can be prevented by given extra pyridoxin to the patients, and the vitamin does not alter the antitubercular activity of INH. This report carried out that pyridoxine does not alter the ratio of free INH to the total INH in blood.

• The Korea Genome Conference
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• 2005.09a
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• pp.45-45
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• 2005

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.45-61
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• 2010

Polymeric based nanomedicines have been developed for diagnosing, treating, and preventing diseases in human body. The nanosized drug delivery systems having various structures such as micelles, nanogels, drug-conjugates, and polyplex were investigated for a great goal in pharmaceutics: increasing therapeutic efficacy for diseases and decreasing drug toxicity for normal tissues. The functional polymers used for constituting these drug delivery systems should have several favorable properties such as stimuli-responsibility and biodegrdability for controlled drug release, and solublization capacity for programmed drug encapsulation. This review discusses recent developments and trends of functional polymers (e.g., pH-sensitive polymers, biodegradable polymers, and cationic polymers) used for nanosized drug carriers.

• Herbal Formula Science
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• v.17 no.2
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• pp.65-72
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• 2009

Objectives : Yukmijihwang-tang (YJT) is known as a tonifying formula for reinforcement of yin deficiency conditions. The present study was carried out to investigate the potential acute toxicity of YJT in ICR male and female mice. Methods : We investigated the acute toxicity about boiling water-extracted YJT. The test article was orally administered once by gavage to 20 male and 20 female mice at dose levels of 0 (control group), 1250, 2500 and 5000 mg/kg body weight. Mortalities, clinical findings, autopsy and body weight changes were monitored daily for the 14 days following the administration according to the Regulation of Korean Food and Drug Administration. Results : We observed survival rates, general toxicity, change of body weight, and autopsy. Single oral administration of YJT with different dosages, no animals died of the test drug. Autopsy of animal revealed no abnormal gross finding. Therefore, $LD_{50}$ value of YJT for ICR mice was more than 5000 mg/kg on oral route. Conclusions : These results suggest that no toxic dose level of YJT in mice is considered to be more than 5000 mg/kg. Consequently, it was concluded that YJT have no effect on acute toxicity and side effect in ICR mice.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.22-24
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• 2003

This presentation briefly will be introduced on new drug approval process and the review of safety and efficacy of drugs in Korea. First, we will present the regulation related to new drug registration [Regulation of the Efficacy and Safety Evaluation of Drugs, etc (Notification No. 2003-17), Standards for Toxicity Test of Drugs, etc(Notification 1999-61) and GLP Regulation for Nonclinical Laboratory Studies (Notification No. 2000-63)] and the regulation related to clinical trial [Guidelines to Clinical Study Authorization for Drugs (Notification No. 2002-65)] and [Korean Good Clinical Practice(KGCP, Notification No. 1999-67) Regulation]. (omitted)

• Bulletin of the Korean Chemical Society
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• v.26 no.7
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• pp.1079-1082
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• 2005

The purpose of this study was to develop a method for increasing the solubility of paclitaxel in water to reduce its toxicity and make the drug more feasible for chemotherapy. A series of highly water soluble paclitaxel polyethylene glycol (PEG) esters were synthesized and evaluated for their anti-tumor activity and toxicity. The solubility of 7-polyethylene glycol paclitaxel carbonate 5 was 840 mg/mL and the acute toxicity ($LD_{50}$) was 286 mg/kg. Because of its reduced toxicity, compound 5 showed a dramatic reduction of tumor volume without any loss of animals in long-term treatment (daily consecutive injections for 15 days).

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.411-416
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• 2018

Chlorpyrifos (CPF) is one of the most heavily used organophosphate pesticides and is useful as an insecticide drug. However, CPF also causes toxic effects in nontarget organisms, including humans and animals. Jageum-Jung (JGJ) is a traditional oriental medicine, composed of five specific herbs with antioxidant and hepatoprotective properties, used for detoxification. In the present study, highly concentrated CPF was orally administrated to male Institute of Cancer Research mice to produce acute toxicity, and the protective effects of JGJ administration were investigated through statistical analysis of changes in body and organ weights and serum biochemical parameters. JGJ caused body and organ weights to recover and reduced the levels of serum biochemical parameters indicative of liver damage, such as glutamic oxalate transaminase, glutamic pyruvate transaminase, alkaline phosphatase, lactic dehydrogenase, urea, glucose, total cholesterol, and triglyceride, that had been increased by CPF treatment. Our results demonstrated that JGJ ameliorates the effects of acute chlorpyrifos-induced toxicity. Therefore, JGJ has the potential to be used as a traditional medicine to alleviate insecticide toxicity.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.56-65
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• 1998

Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently, therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.127-135
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• 2004

Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.