• 한국환경성돌연변이발암원학회지
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• 제24권1호
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• pp.15-18
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• 2004

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• 한국환경성돌연변이발암원학회지
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• 제23권4호
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• pp.131-134
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• 2003

There are significant differences in the extent of drug interactions between subjects. The influence of the genetic make up of drug metabolizing enzyme activities (CYP3A5, CYP2C19 and UDP-glucuronosyl transferase) on the pharmacokinetic drug interaction potential were studied in vivo. Nineteen healthy volunteers were grouped with regard to the $CYP3A5^{*}3$ allele, into homozygous wild-type (CYP3A5^{*}1/1^{*}1$, n=6), heterozygous $(CYP3A5^{*}1/^{*}3$, n=6), and homozygous variant-type $(CYP3A5^{*}3/^{*}3$, n=7) subject groups. The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days), and also following rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. For omeprazole and moclobemide pharmacokinetic interaction study 16 healthy volunteers were recruited. The volunteer group comprised 8 extensive metabolizers and 8 poor metabolizers of CYP2C19, which was confirmed by genotyping. Subjects were randomly allocated into two sequence groups, and a single-blind, placebo-controlled, two-period crossover study was performed. In study I, a placebo was orally administered for 7 days. On the eighth morning, 300 mg of moclobemide and 40 mg of placebo were coadministered with 200 mL of water, and a pharmacokinetic study was performed. During study n, 40 mg of omeprazole was given each morning instead of placebo, and pharmacokinetic studies were performed on the first and eighth day with 300 mg of moclobemide coadministration. In the UGT study pharmacokinetics and dynamics of 2 mg intravenous lorazepam were evaluated before and after rifampin pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between. The subjective and objective pharmacodynamic tests were done before and 1, 2, 4, 6, 8, and 12 hrs after lorazepam administration. The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions. However, during the inhibited metabolic state, the $CYP3A5^{*}3/^{*}3$ group showed a greater decrease in systemic clearance than the $CYP3A5^{*}1/^{*}1$ group $(8.5\pm3.8$ L/h/70 kg vs. $13.5\pm2.7$ L/h/70 kg, P=0.027). The 1'-hydroxymidazolam to midazolam AUC ratio was also significantly lower in the $CYP3A5^{*}3/^{*}3$,/TEX> group $(0.58\pm0.35,$ vs. $1.09\pm0.37$ for the homozygous wild-type group, P=0.026). The inhibition of moclo-bemide metabolism was significant in extensive metabolizers even after a single dose of omeprazole. After daily administration of omeprazole for 1 week, the pharmacokinetic parameters of moclobemide and its metabolites in extensive metabolizers changed to values similar to those in poor metabolizers. In poor meta-bolizers, no remarkable changes in the pharmacokinetic parameters were observed. The area under the time-effect curves of visual analog scale(VAS), choice reaction time, and continuous line tracking test results of lorazepam was reduced by 20%, 7%, 23% respectively in induced state, and in spite of large interindividual variablity, significant statistical difference was shown in VAS(repeated measures ANOVA, p=0.0027).

• 대한정형외과 초음파학회지
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• 제7권1호
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• pp.1-6
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• 2014

목적: 동결견 환자에서 초음파를 통한 검사가 진단 및 치료 후 예후 판단에 객관적 자료로 쓰일 수 있는지 확인하고자, 진단 시 및 스테로이드 주사 치료 후 반대측과 비교 관찰하였다. 대상 및 방법: 저자들은 2012년 7월에서 2013년 7월 사이, line 1(CBT: 오구돌기-이두건)과 line 2(CBG: 오구돌기-이두건 고랑)를 이용한 초음파 검사를 통한 진단을 시행하였다. 대상이 된 20명의 환자에 대해 스테로이드 1회 주사 치료후 그 결과를 2, 4, 6개월의 추시 관찰을 통하여 초음파 연속 검사 상 참고선의 호전 정도 및 견관절 운동 범위 회복 정도를 비교하였다. 결과: 초음파 검사상 환측과 건측의 차이는 치료 전 CBT이 중립, 외회전, 내회전에서 각각 -5.6 mm, -5.0 mm, -4.3 mm였으며 CBG는 -6.1 mm, -4.7 mm, -5.0 mm이었으며(p<0.05), 2개월(CBT: -4.8 mm, -3.5 mm, -2.6 mm/CBG: -4.7 mm, -4.0 mm, -3.6 mm), 4개월(CBT: -4.7 mm, -3.2 mm, -1.7 mm/CBG: -4.3 mm, -3.7 mm, -1.2 mm), 6개월(CBT: -1.1 mm, -2.9 mm, -0.5 mm / CBG: -1.2 mm, -0.7 mm, -0.9 mm)로써 내회전은 4개월, 중립 및 외회전은 6개월 이후 호전되는 소견을 보였다(p<0.05). 운동 범위는 치료 전 전방거상, 외회전, 내회전이 108도, 32도, L5, 2개월에는 117도, 35도, L4, 4개월에는 133도, 42도, L3, 6개월에는 136도, 47도, L2로써 4개월 이후 유의한 회복소견을 보였다. 시각통증등급(VAS)은 치료전 7.5에서 2개월에는 3.0으로 유의한 호전을 보였다(p<0.05). 결론: 스테로이드 주사 치료 후 참고선은 6개월 후 회복되는 소견을 보여, 운동 범위는 4개월 후, 통증은 2개월 후 호전을 보인 것에 비해 다소 지연되어 나타나는 경향이었다. 동적 초음파 검사는 동결견 환자에서 진단 및 예후 판단 시 유효한 검사 방법으로 이용할 수 있을 것으로 생각되었다.