• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.117-123
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• 2011

Loxoprofen sodium, a 2-phenylpropionate non-steroidal anti-inflammatory drug (NSAID), has marked analgesic and antipyretic activities and relatively weak gastrointestinal ulcerogenicity. The purpose of the present study was to evaluate the bioequivalence of two loxoprofen sodium tablets, Hana loxoprofen sodium tablet (Hana Pharm. Co., Ltd.) and Dongwha Loxonin$^{(R)}$ tablet (Dongwha Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of loxoprofen from the two loxoprofen sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Twenty four healthy Korean male volunteers, $22.83{\pm}1.862$ years in age and $69.92{\pm}9.14$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 60 mg as loxoprofen sodium was orally administered, blood samples were taken at predetermined time intervals and the concentrations of loxoprofen in serum were determined using a online column-switching HPLC method with UV/Vis detection. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC^t$, $C_{max}$ and $T_{max}$ were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and un-transformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Dongwha Loxonin$^{(R)}$ tablet, were 2.03, 2.99 and -9.49% for $AUC_t$, $C_{max}$, and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8 to log1.25 (e.g., log0.9831~log1.0535 and log0.9455~log1.1386 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Hana loxoprofen sodium tablet was bioequivalent to Dongwha Loxonin$^{(R)}$ tablet.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.73-80
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• 1997

The bioequivalence of two loxoprofen tablets between the $Loxonin^{TM}$ (Dong Hwa Pharmaceutical Co., Ltd.) and the $Lokpen^{TM}$ (Dong Il Pharmaceutical Co., Ltd.) was evaluated. 12 normal male volunteers (age $21\sim27$ years old) were divided into two groups and a randomized cross-over study was employed. After one tablet containing 60 mg of loxoprofen sodium anhydrous was orally administered, blood was taken at predetermined time intervals and the concentration of loxoprofen in serum was determined with an HPLC method using UV/VIS detector. The pharmacokinetic parameters ($C_{max},\;T_{max}$, and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in $C_{max},\;T_{max}$, and $AUC_t$ between two tablets were $1.13\%,\;0\%,\;and\;0.69\%$, respectively The powers (1-${\beta}$) for $C_{max},\;T_{max}$, and $AUC_t$ were $84.88\%,\;88.61\%,\;and\;84.81\%$, respectively Detectable differences ($\delta$) and confidence intervals were all less than $20\%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Lokpen^{TM}$ tablet is bioequivalent to $Loxonin^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.