• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.89.1-89.8
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• 2018

Objective: Highly effective chemotherapy for patients with low-risk gestational trophoblastic neoplasia (GTN) is associated with almost a 100% cure rate. However, 20%-30% of patients treated with chemotherapy need to change their regimens due to severe adverse events (SAEs) or drug resistance. We examined the treatment outcomes of second-line chemotherapy for patients with low-risk GTN. Methods: Between 1980 and 2015, 281 patients with low-risk GTN were treated. Of these 281 patients, 178 patients were primarily treated with 5-day intramuscular methotrexate (MTX; n=114) or 5-day drip infusion etoposide (ETP; n=64). We examined the remission rates, the drug change rates, and the outcomes of second-line chemotherapy. Results: The primary remission rates and drug resistant rates of 5-day ETP were significantly higher (p<0.001) and significantly lower (p=0.002) than those of 5-day MTX, respectively. Forty-seven patients (26.4%) required a change in their chemotherapy regimen due to the SAEs (n=16) and drug resistance (n=31), respectively. Of these 47 patients failed the first-line regimen, 39 patients (39/47, 82.9%) were re-treated with single-agent chemotherapy, and 35 patients (35/39, 89.7%) achieved remission. Four patients failed second-line, single-agent chemotherapy and eight patients (17.0%) who failed first-line regimens were treated with combined or multi-agent chemotherapy and achieved remission. Conclusions: Patients with low-risk GTN were usually treated with single-agent chemotherapy, while 20%-30% patients had to change their chemotherapy regimen due to SAEs or drug resistance. The second-line regimens of single-agent chemotherapy were effective; however, there were several patients who needed multiple agents and combined chemotherapy to achieve remission.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.289-295
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• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7701-7706
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• 2013

Background: In a prospective cohort study of antiemetic therapy conducted in Malaysia, a total of 94 patients received low emetogenic chemotherapy (LEC) with or without granisetron injections as the primary prophylaxis for chemotherapy-induced nausea and vomiting (CINV). This study is a retrospective cost analysis of two antiemetic regimens from the payer perspective. Materials and Methods: This cost evaluation refers to 2011, the year in which the observation was conducted. Direct costs incurred by hospitals including the drug acquisition, materials and time spent for clinical activities from prescribing to dispensing of home medications were evaluated (MYR 1=$0.32 USD). As reported to be significantly different between two regimens (96.1% vs 81.0%; p=0.017), the complete response rate of acute emesis which was defined as a patient successfully treated without any emesis episode within 24 hours after LEC was used as the main indicator for effectiveness. Results: Antiemetic drug acquisition cost per patient was 40.7 times higher for the granisetron-based regimen than for the standard regimen (MYR 64.3 vs 1.58). When both the costs for materials and clinical activities were included, the total cost per patient was 8.68 times higher for the granisetron-based regimen (MYR 73.5 vs 8.47). Considering the complete response rates, the mean cost per successfully treated patient in granisetron group was 7.31 times higher (MYR 76.5 vs 10.5). The incremental cost-effectiveness ratio (ICER) with granisetron-based regimen, relative to the standard regimen, was MYR 430.7. It was found to be most sensitive to the change of antiemetic effects of granisetron-based regimen. Conclusions: While providing a better efficacy in acute emesis control, the low incidence of acute emesis and high ICER makes use of granisetron as primary prophylaxis in LEC controversial.

• Clinical and Experimental Pediatrics
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• v.57 no.3
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• pp.153-156
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• 2014

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.

• Journal of Pharmaceutical Investigation
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• v.23 no.1
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• pp.27-32
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• 1993

Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

• Journal of Korean Neurosurgical Society
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• v.50 no.5
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• pp.426-433
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• 2011

Objective : The Histoculture Drug Response Assay (HDRA), which measures chemosensitivity using minced tumor tissue on drug-soaked gelfoam, has been expected to overcome the limitations of in vitro chemosensitivity test in part. We analyzed interim results of HDRA in malignant gliomas to see if the test can deserve further clinical trials. Methods : Thirty-three patients with malignant gliomas were operated and their tumor samples were examined for the chemosensitivity to 10 chosen drugs by HDRA. The most sensitive chemotherapy regimen among those pre-established was chosen based on the number of sensitive drugs or total inhibition rate (IR) of the regimen. The response was evaluated by 3 month magnetic resonance image. Results : Among 13 patients who underwent total resection of the tumor, 12 showed no evidence of disease and one patient revealed progression. The response rate in 20 patients with residual tumors was 55% (3 complete and 8 partial responses). HDRA sensitivity at the cut-off value of more than one sensitive drug in the applied regimen showed a sensitivity of 100%, specificity of 60% and predictability of 70%. Another cut-off value of >80% of total IR revealed a sensitivity of 100%, specificity of 69%, and predictability of 80%. For 12 newly diagnosed glioblastoma patients, median progression-free survival of the HDRA sensitive group was 21 months, while that of the non-sensitive group was 6 months ($p$=0.07). Conclusion : HDRA for malignant glioma was inferred as a feasible method to predict the chemotherapy response. We are encouraged to launch phase 2 clinical trial with chemosensitivity on HDRA.

• Tuberculosis and Respiratory Diseases
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• v.38 no.2
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• pp.93-98
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• 1991

A clinical trial was made on 76 patients with pulmonary tuberculosis to determine the effectiveness and acceptibility of 6 month 2SHRZ/4HR antituberculosis regimen. Out of 76 patients, 13 patients (17.1%) dropped out and 11 patients (14.5%) were excluded due to drug resistance. In 3 patients (3.9%), regimen was changed due to adverse effects. Treatment failure rate was 2.0% in 50 patients. One patient, who had far advanced lesion, was treated longer than 6 months due to failure of sputum conversion. The most common adverse effect was arthralgia, which was controlled by the administration of allopurinol and nonsteroidal anti-inflammatory drug. In conclusion, 2SHRZ/4HR for 6 months was effective regimen in treating the newly-diagnosed patients with tuberculosis, but change of the regimen and duration might be carefully considered by the severity of the lesion and adverse effect of the drug But further study will be needed to evaluate not only the efficacy and efficiency of 6 month chemotherapy but also relapse rates.

• Journal of Veterinary Science
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• v.22 no.6
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• pp.41.1-41.14
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• 2021

Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC_0-24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E_max (Hill) equation. The dose was calculated based on the AUC_0-24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 ㎍/mL, 811.99 ± 54.70 ㎍·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 ㎍/mL, 735.85 ± 26.20 ㎍·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 ㎍/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC_0-24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions: A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.

• 대한예방의학회:학술대회논문집
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• 1994.02b
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• pp.332-335
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• 1994

Compared to other variables being considered in therapeutics, patient compliance has long been given minor attention although it affects every aspect of medical care; Limited methodology of compliance measurement, in particular, has hampered major progress in research, and pre-conceptions have been reiterated. However, there is a recent surge in interest derived from new data revealed by reliable methods, i.g. continuous medication (compliance) monitoring. The visualization of dynamics in drug regimen compliance over time offers unique opportunities, both to scientific drug evaluation and therapeutics in medical practice. New perspectives related to the descriptive and explanatory side of the problem are outlined by giving examples from various therapeutic fields.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.113-117
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• 1996

This study was attempted to investigate the pharmacokinetic interaction between sodium valproate (4, 8, 16 mg/kg, i.v.) and phenytoin (4 mg/kg, i.v.) in rabbits. The plasma concentration and area under the curve (AUC) of phenytoin were increased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (4, 8, 16 mg/kg) in rabbits. The volume or distribution and total body clearance of phenytoin were decreased significantly (p<0.05, p<0.01) when coadministered with sodium valproate (8, 16 mg/kg) in rabbit. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin will be coadministered with sodium valproate in clinical use.