• Toxicological Research
• /
• v.17 no.2
• /
• pp.159-161
• /
• 2001

The anti-emetic effect of a 5-HT$_3$ receptor antagonist, Ondaron, was compared with that of the approved ondansetron agent, Zofran$\circledR$ in the ferrets. Emesis was induced by single intraperitoneal injection of cisplatin 10 mg/kg, and Ondaron or Zofran$\circledR$ was injected intraperitoneally in a dose of 1.0 mg/kg, respectively. Ondaron and Zofran$\circledR$ effectively antagonised the emetic response for 4 hours after injection. They significantly reduced the number of vomiting and retching, and prolonged the latency to the first episode. The anti-emetic effect of Ondaron was almost the equal to that of Zofran$\circledR$. These results suggest that Ondaron is an effective anti-emetic agent against cisplatin-induced emesis, and its anti-emetic potency is similar to that of 5-$HT_3$ receptor abtagonist, Zofran$\circledR$.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.3
• /
• pp.213-218
• /
• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.

• Biomolecules & Therapeutics
• /
• v.11 no.1
• /
• pp.58-64
• /
• 2003

Ondansetron is a potent, highly selective 5-hydroxytryptamin $e_3$(5-H $T_3$) receptor-antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, Zofran (Glaxo Smithcline Korea Ltd.) and Onfran (Korea United Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 24.39$\pm$1.69 year in age and 69.00$\pm$6.74kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 8mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AVC, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC, $C_{max}$ and T max between two tablets were 5.83％, 5.75％ and －5.71％, respectively when calculated against the Zofran, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were above 90％, above 90％ and below 60％, respectively. Minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 were less than 20％ (e.g., 12.74％ and 11.78％ for AUC and $C_{max}$ respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20％ (e.g., 34.22％). The 90％ confidence intervals were within $\pm$20％ (e.g., -2.73∼14.39 and -2.16∼13.67 for AUC and $C_{max}$ respectively). But 90％ confidence intervals for $T_{max}$ were not within $\pm$20％ (e.g., -28.71∼17.28). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant difference in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20％ (e.g., 5.83％ and 5.75％ for AUC and $C_{max}$ respectively). The 90％ confidence intervals for the log transformed data were the acceptance range of log 0.8 to log 1.25 (e.g., log 0.99∼log 1.15 and log 0.98∼log 1.15 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$, met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofrm1 tablet.t is bioequivalent to Zofrm1 tablet.m1 tablet.m1 tablet.m1 tablet.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.414.1-414.1
• /
• 2002

To improve the compliance of oral administration of drugs in cancer patients, who are unable to swallow tablets, FDT containing ondansetron HCI($Onseran^{TM}$) was developed with a low-cost manufacturing process. $Onseran^{TM}$ was prepared from ondansetron. mannitol, crospovidone. and others with a direct compression method. The disintegration time and dissolution rate of $Onseran^{TM}$ were assessed according to the USP method. The results were compared with those of the reference drug ($Zofran^{TM}$). (omitted)

• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.127-135
• /
• 2001

Purpose : This study is a prospective randomized clinical trial comparing the efficacy and complication of anti-emetic drugs for prevention of nausea and vomiting after radiotherapy which has moderate emetogenic potential. The aim of this study was to investigate whether the anti-emetic efficacy of ondansetron $(Zofran^{\circledR})$ 8 mg bid dose (Group O) is better than the efficacy of metoclopramide 5 mg lid dose (Group M) in patients undergoing fractionated radiotherapy to the abdominal region. Materials and Methods : Study entry was restricted to those patients who met the following eligibility criteria: histologically confirmed malignant disease; no distant metastasis; performance status of not more than ECOG grade 2; no previous chemotherapy and radiotherapy. Between March 1997 and February 1998, 60 patients enrolled in this study. All patients signed a written statement of informed consent prior to enrollment. Blinding was maintained by dosing identical number of tablets including one dose of matching placebo for Group O. The extent of nausea, appetite loss, and the number of emetic episodes were recorded everyday using diary card. The mean score of nausea, appetite loss and the mean number of emetic episodes were obtained in a weekly interval. Results : Prescription error occurred in one patient. And diary cards have not returned in 3 patients due to premature refusal of treatment. Card from one patient was excluded from the analysis because she had a history of treatment for neurosis. As a result, the analysis consisted of 55 patients. Patient characteristics and radiotherapy characteristics were similar except mean age was $52.9{\pm}11.2$ in group M, $46.5{\pm}9.5$ in group O. The difference of age was statistically significant. The mean score of nausea, appetite loss and emetic episodes in a weekly interval was higher in group M than O. In group M, the symptoms were most significant at 5th week. In a panel data analysis using mixed procedure, treatment group was only significant factor detecting the difference of weekly score for all three symptoms. Ondansetron $(Zofran^{\circledR})$ 8 mg bid dose and metoclopramide 5 mg lid dose were well tolerated without significant side effects. There were no clinically important changes In vital signs or clinical laboratory parameters with either drug. Conclusion : Concerning the fact that patients with younger age have higher emetogenic potential, there are possibilities that age difference between two treatment groups lowered the statistical power of analysis. There were significant difference favoring ondansetron group with respect to the severity of nausea, vomiting and loss of appetite. We concluded that ondansetron is more effective anti-emetic agents in the control of radiotherapy-induced nausea, vomiting, loss of appetite without significant toxicity, compared with commonly used drug, i.e., metoclopramide. However, there were patients suffering emesis despite the administration of ondansetron. The possible strategies to improve the prevention and the treatment of radiotherapy-induced emesis must be further studied.

• Journal of Pharmaceutical Investigation
• /
• v.28 no.1
• /
• pp.35-42
• /
• 1998

A $3{\times}3$ Latin square crossover study for the bioequivalence of three ondansetron formulations was conducted. Test products were $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg tablets and reference product was $Zofran^{\circledR}$ tablet. Twenty one healthy Korean male subjects received each formulation at the ondansetron dose of 8 mg and plasma concentrations of ondansetron were monitored by HPLC for over a period of 12 hr after the oral administration. Statistical procedure for bioequivalence evaluation of AUC {e.g., analysis of variance (ANOVA), multiple comparison and confidence intervals} was carried out. There were no significant differences in AUC among the formulations. The confidence intervals for the AUC of $Vominon^{\circledR}$ 8 mg and $Vominon^{\circledR}$ 4 mg were between -0.24 and 15.54% and between -2.41 and 13.36% respectively, within a range that proposed by the Korea Food and Drug Administration Guidelines for Bioequivalence. These statistical procedure could be standardized and generally applicable for the assessment of bioequivalence for multiple (more than two) formulations.

• Biomolecules & Therapeutics
• /
• v.11 no.1
• /
• pp.65-71
• /
• 2003

Terbinafine is a synthetic allylamine that is available in an oral formulation and is used at a dosage of 250mg/day. It is used as an active antifungal agent and inhibits the fungal enzyme squalene epoxidase, which leads to the accumulation of the sterol squalene, which is toxic to the organism. The purpose of the present study was to evaluate the bioequivalence of two terbinafine tablets, Lamisil (Novartis Korea Ltd.) and Terbinex (C-TRI Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 26.00$\pm$2.57 year in age and 70.51$\pm$9.36 kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 125 mg of terbinafine was orally administered, blood was taken at predetermined time intervals and the concentrations of terbinafine in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AUC, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUC, $C_{max}$ and $T_{max}$ between two tablets were －4.191％, 5.223％ and －25.720％, respectively when calculated against the Lamisil, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were 81％, 87％ and below 60％, respectively. Minimum detectable differences(.il) at alpha=O.1 and 1-/3=0.8 were less than 20％ (e.g., 19.72％ and 17.77％ for AUC and $C_{max}$, respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20％ (e.g., 26.25％). The 90％ confidence intervals were within $\pm$20％ (e.g., －17.440∼9.06 and －6.713∼17.160 for AUC and $C_{max}$ respectively). But 90％ confidence intervals for $T_{max}$ were not within $\pm$20％ (e.g., －43.346∼8.083). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant differences in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20％ (e.g., －4.19％ and 5.22％ for AUC and $C_{max}$, respectively). The 90％ confidence intervals for the log transformed data were not the acceptance range of log 0.8 to log 1.25 in AUC but the acceptance range of log 0.8 to log 1.25 in $C_{max}$ (e.g., log 1.13∼log 1.50 and log 0.94-log 1.22 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA (1998 year) for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofran tablet. But in another ANOVA test AUC did not meet the criteria of KFDA (2002) for bioequivalence but $C_{max}$ met the criteria of KFDA (2002 year) for bioequivalence.or bioequivalence.equivalence.equivalence.equivalence.