가바펜틴 400밀리그람 캡슐의 생물학적동등성시험 (Bioequivalence Test of Gabapentin 400 mg Capsules)

서지정보

· 발행기관 : 대한약학회
· 수록지 정보 : 약 학 회 지 / 52권 / 3호 / 195 ~ 200페이지
· 저자명 : 김세미, 강현아, 조혜영, 신새벽, 류희두, 윤화, 이용복

초록

Gabapentin, [1-(aminomethyl) cyclohexaneacetic acid], a structural analog of γ-aminobutyric acid (GABA), is
being developed for the treatment of epilepsy. Unlike GABA, gabapentin crosses the blood-brain barrier after systemic
administration. Gabapentin is an effective antiepileptic drug in patients with partial and secondarily generalized seizures who
are uncontrolled with use of existing anticonvulsant drug therapy. The purpose of the present study was to evaluate the
bioequivalence of two gabapentin 400 mg capsules, Neurontin® capsule 400 mg (Pfizer Inc.) and Gabatin capsule 400 mg
(Korean Drug Co. Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of
gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with various dissolution
media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, 23.58±1.50 years in age and
66.74±8.31 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After
one capsule containing 400 mg as gabapentin were orally administered, blood was taken at predetermined time intervals and
the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles
of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as AUCt,
Cmax and Tmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically
transformed AUCt, Cmax and untransformed Tmax. The results showed that the differences between two formulations
based on the reference drug, Neurontin® capsule 400 mg, were 2.04, -3.68 and 16.79% for AUCt, Cmax and Tmax,
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 0.91~log 1.16 and
log 0.87~log 1.11 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied,
indicating Gabatin capsule 400 mg was bioequivalent to Neurontin® capsule 400 mg.

영어초록

Gabapentin, [1-(aminomethyl) cyclohexaneacetic acid], a structural analog of γ-aminobutyric acid (GABA), is
being developed for the treatment of epilepsy. Unlike GABA, gabapentin crosses the blood-brain barrier after systemic
administration. Gabapentin is an effective antiepileptic drug in patients with partial and secondarily generalized seizures who
are uncontrolled with use of existing anticonvulsant drug therapy. The purpose of the present study was to evaluate the
bioequivalence of two gabapentin 400 mg capsules, Neurontin® capsule 400 mg (Pfizer Inc.) and Gabatin capsule 400 mg
(Korean Drug Co. Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of
gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with various dissolution
media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, 23.58±1.50 years in age and
66.74±8.31 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. After
one capsule containing 400 mg as gabapentin were orally administered, blood was taken at predetermined time intervals and
the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles
of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as AUCt,
Cmax and Tmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically
transformed AUCt, Cmax and untransformed Tmax. The results showed that the differences between two formulations
based on the reference drug, Neurontin® capsule 400 mg, were 2.04, -3.68 and 16.79% for AUCt, Cmax and Tmax,
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 0.91~log 1.16 and
log 0.87~log 1.11 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied,
indicating Gabatin capsule 400 mg was bioequivalent to Neurontin® capsule 400 mg.

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