• Journal of Gastric Cancer
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• v.4 no.2
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• pp.59-74
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• 2004

This report attempts to explain the (i) implications of comorbidity for research and practice in the fieldo of oncology, (ii) the approach for dosing of anti-cancer drugs in the presence of comorbidity, as an example of its clinical application, and finally (iii) the dosing guidelines for the anticancer drugs clinically active in gastric cancer in the presence of renal or liver dysfunction. This has resulted from the idea of approaching comorbidity in a systematic way and of integrating it with oncologic decisions. Various methods have been used to assess comorbidity. However, significant work remains to be done to analyze how various diseases combine to influence the oncologic outcome. The main end-point explored so far has been mortality, but a largely open challenge remains to correlate comorbidity with treatment tolerance and functional and quality of life, as well as to integrate it in clinical decision-making. Cancer chemotherapy in comorbidity should be considered as an example of the need for dose optimization in individual patients, and it should be determined by considering the basic principles of the pharmacokinetics and the pharmacodynamics of the agents. This review analyzes the available data on the pharmacokinetics and the toxicities of anti-cancer agents in the comorbidity population.

• YAKHAK HOEJI
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• v.57 no.6
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• pp.412-419
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• 2013

Drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than $ 1billion to bring a molecule from discovery to market. Compounds fail for various reasons but one of the significant reasons that accounts for failures in clinical trials is poor prediction/understanding of pharmacokinetics and drug metabolism in human. In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic properties in human, drug metabolism, pharmacokinetic scientists have been continually developing new technologies and compound screening strategies. Over the last few years, accelerator mass spectrometry (AMS) and its applications to preclinical/clinical pharmacokinetics and ADME studies have significantly increased, particularly for new chemical/biological entities that are difficult to support with conventional radiolabel studies. In this review, the application of AMS for micro-dosing, micro-tracer absolute bioavailability, mass balance and metabolite profiling studies will be discussed.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.113-118
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• 2000

In order to assay the efficacy of newly synthesized antiviral compounds, pyrimidine analogs, pharmacokinetics of those were established as compared with already marketed zidovudine. Zidovudine (15, 20, 25 and 35 mg/kg), LJ142 (18.52 mg/kg) and LJ143 (15, 18.52 and 30 mg/kg) were administered orally and intravenously in rats, blood samples were collected post-injection(i.e., for 360 min) at appropriate time intervals. Those were analyzed by HPLC with UV detection at 265 nm. Pharmacokinetic parameters $(C_{max},\;T_{1/2},\;MRT,\;AUC,\;AUMC,\;Vd_{SS},\;Cl_t)$ were calculated. AUCs of zidovudine and LJ143 following I.V. dosing of $15{\sim}25\;mg/kg\;and\;15{\sim}18.18\;mg/kg$ were dose-independent. However, AUCs of zidovudine and LJ43 following I.V. dosing of $25{\sim}35\;mg/kg\;and\;18.18{\sim}30\;mg/kg$ were dose-dependent. The relative bioavailability of zidovudine, LJ142 and LJ143 following oral administration were 61.94, 46.44 and 78.24%, respectively.

• Korean Journal of Veterinary Service
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• v.25 no.3
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• pp.299-308
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• 2002

The purposes of this study were to characterize the disposition of sulfathiazole(ST) and to investigate the effects of sodium bicarbonate on the disposition of ST in broiler chicks(2.5～3.0kg). Animals were given ST acutely(10～80mg/kg, PO), and plasma, kidney, muscle, heart, liver and spleen samples were collected and analyzed for ST by high performance liquid chromatography. The plasma and tissue data was consistent with a one-compartment pharmacokinetic model. The drug is rapidly but incompletely(2.5～3.87%) absorbed with peak plasma and tissue levels being achieved within one hour after dosing. The plasma and tissue levels depended on drug dosage, and the descending order in concentration of ST was kidney > plasma > heart > muscle $\geq$ spleen $\geq$ liver from animals sacrificed at one hour after dosing. Moreover, significant positive correlations(r>0.9) existed between plasma and tissue levels of ST. In addition, sodium bicarbonate pretreatment decreased plasma level, indicating that an alkalinization stimulate the excretion of ST. Results of this study suggest that oral application of ST was rapidly absorbed and eliminated, and confirmed that tissue residues of ST can be estimated from plasma drug concentration in broiler chicks.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.4
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• pp.980-990
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• 2003

The effect of Gamigyuibi-tang on the penile erection induced by apomorphine HCI and on the erectile dysfunction induced by p,p-DDE, an environmental hormone derivate of DOT, were monitored using male cats. The changes of penile length, diameter, erectic periods and histological profiles of corpus cavernosum and corpus spongiosum were observed with blood testosterone levels. In conclusion, dose-dependent and significant increase of penile length, diameter, erectic periods and blood testosterone levels were detected in the Gamigyuibitang-dosing groups compared to other groups. In addition, it is also demonstrated that the increasement of congestion of blood vessels and dilation of connective tissues, and decreasement of adipocytes in the corpus cavernosum and/or corpus spongiosum of the Gamigyuibitang-dosing groups. According to these results, it is considered that Gamigyuibitang has some augmentation effect against to apomorphine HCI inducing penile erection and it also suggested that Gamigyuibitang has favorable effect to treatment of erectic dysfunctions induced by p,p-DDE.

• Archives of Pharmacal Research
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• v.8 no.3
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• pp.177-186
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• 1985

Effect of food on the absorption characteristics of oral rifampicin was studied in the fasted rats. Rifampicin dissolved in a new cosolvent was also injected to the rats intravenously, and the pharmacokinetic analysis was performed to explain the effect of food on the gastrointestinal absorption of rifampicin. Rifampicin was absorbed rapidly and completely in the fasting state. Food had a profound effect on the gastrointestinal absorption of rifampicin, i. e., bioavailability and the extent of absorption were decreased to less than one-third of the fasting state in the postprandial state. Food seemed to imhibit the absorption and reabsorption of rifampicin in the gastrointestinal tract, but not the absorption rate constant. Hepatobiliary excretion seemed to be the major route of elimination, since the renal clearance accounted for only 8 % of the systemic clearance. Nevertheless, first-pass effect was negligibly small and most of rifampicin absorbed could reach systemic circulation. Serum concentration change of oral rifampicin on multiple dosing differed markedly in the fasting and postprandial state, which suggested the need of careful adjustment of dosage regimen in both states.

• Biomolecules & Therapeutics
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• v.5 no.1
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• pp.100-105
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• 1997

DW-166HC ($^{166}$Holmium-chitosan) is a complex of $^{166}$Ho, $\beta$- and $\gamma$-ray emitter, and chitosan, a polymer of glucosamine, with radiotherapeutic potential. The current study was performed to determine the acute toxicities of $^{165}$Ho-chitosan in mice by two different routes of administration. The both sex mice were given a single intravenous bolus injection of $^{165}$Ho-chitosan complex at doses of 12, 10, 6, 5 and 4 mg/kg or subcutaneous administration at doses of 600, 500, 400 and 300 mg/kg. Chitosan was dosed to control animals as 16 and 800 mg/kg, intravenously and subcutaneously, respectively. The doses of $_{165}$Ho-chitosan complex were expressed as $_{165}$holmium nitrate pentahydrate and the ratio of $^{165}$Ho$(NO_3)_3$).$5H_2O$ to chitosan was 3/4 Severe convulsion and respiratory failure were followed by death within 10 min after intravenous dosing. Transient unilateral hindlimb hypokinesias were found in two mice of 5 mg/kg dosing group during the study period. No abnormalities were observed during the necropsy of survived animals in intravenous dosing group. Only one male animal was found dead in 500 mg/kg subcutaneously dosed group. Alopecia with or without cutaneous ulcer were found in most mice including control animals. During necropsy, omental adhesion was observed in all dose ranges and enlarged spleen was found in several animals including control group. It is suggested that the acute intravenous >).$LD_{50}s$ for male and female mice were 4.90 and 6.03 mg/kg, respectively. The lowest lethal dose in male was 500 mg/kg by subcutaneous administration.

• Journal of Korean Society of Environmental Engineers
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• v.36 no.7
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• pp.483-491
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• 2014

In this study, we developed an M-COS (molit coagulant-dosing optimization system), which enables to apply the optimum coagulant dose determined in real time, in order to satisfy the total phosphorus (TP) regulation (0.5 mg/L), and then tested its field applicability. Field tests were conducted at three different periods in 2014 in a pilot plant where the M-COS was installed. Coagulant reduction rate by the M-COS was 10.4%, 15.3%, and 9.0% for each period (average 11.6%), when comparing with a control where coagulants were applied at a constant rate. Total cost for the M-COS or control was estimated by summing up the coagulant cost and sludge treatment cost, and then the resulting cost increase was predicted. Cost reduction rate by the M-COS was 13.8%, 20.0%, and 11.4% for each period (average 15.0%). This study indicates that the M-COS can be an alternative to a conventional system for TP treatment, with a better cost efficiency.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.409-416
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• 1993

In the method for lithium (Li) analysis, flame emission photometry and atomic absorption spectrophotometry (AAS) have been used most frequently. In addition, lithium can be analyzed by ion-selective electrode (ISE) or fluorscence polarization immunoassay. We evaluated the comparison between AAS method based on the principle of absorption of light at 670.8 nm by Li and ISE method based on the principle of voltage difference generated by Li in contact with lithium ionophore. We compared with those obtained by AAS (AA/AE Spectrophotometer 551, Instrumentation Laboratory Co.) and ISE(CSYNCHRON EL-ISE, Beckman Co.) in the serum and urine of 6 patients and evaluated time-related changes of serum lithium concentration after dosing in both methods. The results are summarized as follows : 1. In within-run precision study for lithium concentration, coefficient variations (CVs, %) ranged from 1.34 to 2.17 for AAS and from 0.34 to 0.85 for ISE method. In between-run precision study for lithium concentration, CVs ranged from 1.23 to 1.72 for AAS and from 0.61 to 1.38 for ISE method. 2. The correlation study between AAS and ISE method resulted in Y=0.946X+0.137 (N=32, r=0.933, X=AAS, Y=ISE) for serum lithium and Y=1.092X+0.977 (N=28, r=0.943, X=AAS, Y=ISE) for urine lithium. 3. Time-related changes of serum lithium concentration in both AAS and ISE method resulted in peak serum levels about 2 hours after dosing and then rapidly decreased after the peak serum level and finally arrived at nearly initial levels about 9 hours after dosing. 4. The reference range of serum lithium was found as undetectable level for both AAS and ISE method and the reference range of urine lithium to the urine creatinine was 0-0.00014 mmol/mg(mean 0.00002 mmol/mg) for AAS method.

• Korean Journal of Veterinary Research
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• v.31 no.4
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• pp.367-379
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• 1991

The purpose of this study was to investigate the effect of antioxidants (vitamin E, selenium, and coenzyme $Q_{10}$) on the bleomycin-induced pulmonary lesions in male rats. Sprague-Dawley male rats were divided into 4 treatment groups ($T_1$, $T_2$, $T_3$, $T_4$) and 4 control groups ($C_1$, $C_1$, $C_3$, $C_4$). The treatment groups of rats weie given a single intratracheal dose of bleomycin (1.5 units/rat) and control groups of rats were given a single intratracheal dose of normal saline (0.15ml/rat). The rats in the $T_1$ group and $C_1$, group were dosed with normal saline (0.5ml/kg/day), the rats in the $T_2$ group and $C_2$ group were dosed with vitamin E (50mg/kg/day), the rats in the $T_3$ group and $C_3$ group were dosed with sodium selenite (3mg/kg/day) and the rats in the $T_4$ gronp and $C_4$ group were dosed with coenzyme $Q_{10}$ (2.5mg/kg/day) intraperitoneally for 7 days or 14 days, respectively. Animals were killed at 7th and 14th day after dosing with bleomycin or saline. The results obtained were as follows: 1. Lung wet weight of treatment groups of rats was increased significantly while body weight gain of them was decreased significantly in comparison with that of control groups of rats (p<0.01). 2. The ratio(%) of lung wet weight to final body weight of treatment groups of rats was increased significantly in comparison with that of control groups of rats (p<0.01). 3. The main histopathological findings of lungs observed in rats at 7th day after dosing with bleomycin were proliferation of the type II alveolar epithelial cells and fibroblasts, increased invading of macrophages into lesions, round cell infiltration and perivascular edema. 4. Lung fibrous tissues were markedly increased in rats observed at 14th day after dosing with bleomycin. 5. Pumonary lesions observed in rats dosed with bleomycin and antioxidants(vitamin E, selenium, coenzyme $Q_{10}$) were not significantly different from those of rats given bleomycin alone.