• Journal of Pharmaceutical Investigation
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• v.37 no.3
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• pp.197-203
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• 2007

A bioequivalence study of $Dilast^{TM}$ Capsule (Chong Kun Dang Pharma. Co., Ltd.) to $Ketas^{(R)}$ Capsule (Han Dok Pharma. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty eight healthy male Korean volunteers received each medicine at the ibudilast dose of 20 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of ibudilast were monitored by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t\;and\;C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Dilast^{TM}$ $Capsule/Ketas^{(R)}$ Capsule were $log0.93{\sim}log1.06$ and $log0.93{\sim}log1.11$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Dilast^{TM}$ Capsule and $Ketas^{(R)}$ Capsule with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.117-123
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• 2010

Ibudilast, 3-isobutyryl-2-isopropyrazolo[1,5-a]pyridine, is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). It preferentially inhibits PDE 3A, PDE4, PDE10 and PDE11 as well as a number of the other PDE families, albeit to a lesser extent. Ibudilast is used clinically to treat bronchial asthma and cerebrovascular disorders. Thes e clinical uses are based on the ability of ibudilast to inhibit platelet aggregation, improve cerebral blood flow and attenuate allergic reactions. The purpose of the present study was to evaluate the bioequivalence of two ibudilast capsules, Ketas capsule (Handok Pharmaceuticals Co., Ltd.) and Pinatos capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of ibudilast from the two ibudilast formulations was tested using KP Apparatus method with various dissolution media. Twenty six healthy male subjects, 23.31${\pm}$1.09 years in age and 70.45${\pm}$8.51 kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 10 mg as ibudilast was orally administered, blood samples were taken at predetermined time intervals and the concentrations of ibudilast in serum were determined using HPLC/UV detector. 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 untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, Ketas, were 6.99%, -2.48% and 9.93% 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 log 0.8 to log 1.25 (e.g., log 0.8791~log 1.1861 and log 0.8347~log 1.1199 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Pinatos capsule was bioequivalent to Ketas capsule.