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Effect of food on pharmacokinetics of 3,4-Diaminopyridine in rats and healthy volunteers
Abstracts / Journal of the Neurological Sciences 333 (2013) e422–e480
Conclusion: Achieving a status of MM or better by maximum PSL dose or reduced PSL dose combined with other agent may improve the present MG status and QOL.
doi:10.1016/j.jns.2013.07.1533
Abstract - WCN 2013 No: 563 Topic: 7 - Neuromuscular disorders Effect of food on pharmacokinetics of 3,4-Diaminopyridine in rats and healthy volunteers N. Ishidaa,b, E. Kobayashic, R. Matsushitab, K. Komaid. a Department of Pharmacy, National Hospital Organization Iou Hospital, Kanazawa, Japan; bGraduate School of Natural Science and Technology, Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; cDepartment of Pharmacy, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan; dDepartment of Neurology, National Hospital Organization Iou Hospital, Kanazawa, Japan Background: 3,4-Diaminopyridine (3,4-DAP) is commonly used to treat neuromuscular diseases such as Lambert–Eaton myasthenic syndrome and multiple sclerosis; however, the pharmacokinetics of 3,4-DAP is not well understood. Objective: We aimed to investigate the effect of food on the pharmacokinetics of 3,4-DAP in rats and humans. In addition, we aimed to study the effect of food on the intestinal absorption of 3,4-DAP in rats. Material and methods: We administered single 3,4-DAP doses of 10 mg/kg orally or 2 mg/kg intravenously to Wistar male rats (n = 4– 7) and 10 mg 3,4-DAP to healthy volunteers (n = 5) in the fasting state and after meals. The intestinal absorption rate of 3,4-DAP was estimated by using a in situ closed loop method in rats. Results: The areas under the serum concentration time curve for 3,4-DAP significantly decrease by food intake, and the corresponding bioavailability values were also significantly decrease from 25.1% ±4.0% to12.1% ± 0.8% (mean ± SD; P b 0.01) in rats. In the healthy volunteers, fasting might have reduced the time to reach the maximum serum concentration (Cmax) of 3,4-DAP and elevated Cmax. In situ close loop method, food reduced the intestinal absorption rate of 3,4-DAP by 5–10%. Conclusion: These studies showed that food intake lowered the absorption of 3,4-DAP. Therefore, the administration of 3,4-DAP without food might be a candidate of improvement of the effect. doi:10.1016/j.jns.2013.07.1534
Abstract - WCN 2013 No: 660 Topic: 7 - Neuromuscular disorders Clinical picture of anti-MuSK-antibody-positive juvenile myasthenia gravis in Japan R. Nakataa, M. Motomuraa, H. Shiraishia, T. Naritaa, T. Yoshimurab, A. Kawakamia, M. Tsujihatac. aDepartment of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki, Japan; b School of Health Science, Nagasaki University, Nagasaki, Japan; cNagasaki Kita Hospital, Nagasaki, Japan Objective: The present study aimed to determine the characteristics of anti-muscle-specific receptor tyrosine kinase (MuSK)-antibodypositive juvenile myasthenia gravis (JMG) (onset before age 15). Information on JMG is limited, and they are reported to be clinically and immunologically distinct from adult onset myasthenia gravis (MG). Patients and methods: Four patients were positive for anti-MuSKantibody among 28 patients collected nationwide from 2006 through
e427
2009 for antibody assay in our institute. We investigated the clinical characteristics and measured IgG subclasses in these patients. Results: All four patients presented generalized MG with relatively severe clinical course. There were no thymus abnormalities. IgG subclass was dominantly of IgG4 subclass. Conclusions: The clinical characteristics and clinical course of antiMuSK-antibody-positive JMG differ from general JMG or adult-onset MG. doi:10.1016/j.jns.2013.07.1535
Abstract - WCN 2013 No: 612 Topic: 7 - Neuromuscular disorders Baff (B cell activating factor) can be the clinical marker in myasthenia gravis W. Sakaia, S. Nakaneb, T. Naritac, M. Motomurac, H. Matsuoa. aDepartment of Neurology, Nagasaki Kawatana Medical Center, Higashisonogi, Japan; b Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; cDepartment of Clinical Neuroscience and Neurology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Background: Myasthenia gravis (MG) is an antibody mediated disease in which the target autoantigen is the acetylcholine receptor (AChR) at the postsynaptic membrane of the neuromuscular junction. B cell activating factor (BAFF) is the potent B cell survival factor and is necessary for peripheral B cell differentiation and maturation. Excess BAFF promotes the survival and growth of autoreactive B cells. The previous studies have shown that serum BAFF levels in patients with MG are higher than in control subjects. BAFF may play an important role in the pathogenesis of MG. Objective: To compare serum BAFF levels in patients with AChR antibody positive MG (AChR MG) and muscle specific kinase antibody positive MG (MuSK MG). Patients and methods: We retrospectively analyzed 14 ocular AChR MG, 31 generalized AChR MG and 25 MuSK MG. We compared the serum BAFF levels with the clinical characteristics among 3 groups. Results: The serum BAFF levels in generalized AChR MG (1559.6 ± 108.6 pg/mL) were significantly higher than in MuSK MG (568.1 ± 36.3 pg/mL) and ocular AChR MG (598.1 ± 65.9 pg/mL). There was a correlation between the serum BAFF levels and disease severity in AChR MG. The serum BAFF levels of the generalized AChR MG with thymic abnormalities (1536.4 ± 728.8 pg/mL) were statistically higher than the ocular AChR MG. Conclusion: The serum BAFF levels are increased in patients with generalized AChR MG compaired to MuSK MG and ocular AChR MG. doi:10.1016/j.jns.2013.07.1536
Abstract - WCN 2013 No: 643 Topic: 7 - Neuromuscular disorders Autosomal recessive limb girdle muscular dystrophy: Prospective study and characterisation of 280 cases by immunohistochemistry and immunoblotting A. Nalini. Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India Background: ARLGMD is a common disorder in Southern India due to high consanguinity. Objective: To study pattern of ARLGMD in India. Materials and methods: Prospective study of 300 cases seen between February 2010 and October 2012. All suspected cases of ARLGMD
Conclusion: Achieving a status of MM or better by maximum PSL dose or reduced PSL dose combined with other agent may improve the present MG status and QOL.
doi:10.1016/j.jns.2013.07.1533
Abstract - WCN 2013 No: 563 Topic: 7 - Neuromuscular disorders Effect of food on pharmacokinetics of 3,4-Diaminopyridine in rats and healthy volunteers N. Ishidaa,b, E. Kobayashic, R. Matsushitab, K. Komaid. a Department of Pharmacy, National Hospital Organization Iou Hospital, Kanazawa, Japan; bGraduate School of Natural Science and Technology, Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; cDepartment of Pharmacy, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan; dDepartment of Neurology, National Hospital Organization Iou Hospital, Kanazawa, Japan Background: 3,4-Diaminopyridine (3,4-DAP) is commonly used to treat neuromuscular diseases such as Lambert–Eaton myasthenic syndrome and multiple sclerosis; however, the pharmacokinetics of 3,4-DAP is not well understood. Objective: We aimed to investigate the effect of food on the pharmacokinetics of 3,4-DAP in rats and humans. In addition, we aimed to study the effect of food on the intestinal absorption of 3,4-DAP in rats. Material and methods: We administered single 3,4-DAP doses of 10 mg/kg orally or 2 mg/kg intravenously to Wistar male rats (n = 4– 7) and 10 mg 3,4-DAP to healthy volunteers (n = 5) in the fasting state and after meals. The intestinal absorption rate of 3,4-DAP was estimated by using a in situ closed loop method in rats. Results: The areas under the serum concentration time curve for 3,4-DAP significantly decrease by food intake, and the corresponding bioavailability values were also significantly decrease from 25.1% ±4.0% to12.1% ± 0.8% (mean ± SD; P b 0.01) in rats. In the healthy volunteers, fasting might have reduced the time to reach the maximum serum concentration (Cmax) of 3,4-DAP and elevated Cmax. In situ close loop method, food reduced the intestinal absorption rate of 3,4-DAP by 5–10%. Conclusion: These studies showed that food intake lowered the absorption of 3,4-DAP. Therefore, the administration of 3,4-DAP without food might be a candidate of improvement of the effect. doi:10.1016/j.jns.2013.07.1534
Abstract - WCN 2013 No: 660 Topic: 7 - Neuromuscular disorders Clinical picture of anti-MuSK-antibody-positive juvenile myasthenia gravis in Japan R. Nakataa, M. Motomuraa, H. Shiraishia, T. Naritaa, T. Yoshimurab, A. Kawakamia, M. Tsujihatac. aDepartment of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki, Japan; b School of Health Science, Nagasaki University, Nagasaki, Japan; cNagasaki Kita Hospital, Nagasaki, Japan Objective: The present study aimed to determine the characteristics of anti-muscle-specific receptor tyrosine kinase (MuSK)-antibodypositive juvenile myasthenia gravis (JMG) (onset before age 15). Information on JMG is limited, and they are reported to be clinically and immunologically distinct from adult onset myasthenia gravis (MG). Patients and methods: Four patients were positive for anti-MuSKantibody among 28 patients collected nationwide from 2006 through
e427
2009 for antibody assay in our institute. We investigated the clinical characteristics and measured IgG subclasses in these patients. Results: All four patients presented generalized MG with relatively severe clinical course. There were no thymus abnormalities. IgG subclass was dominantly of IgG4 subclass. Conclusions: The clinical characteristics and clinical course of antiMuSK-antibody-positive JMG differ from general JMG or adult-onset MG. doi:10.1016/j.jns.2013.07.1535
Abstract - WCN 2013 No: 612 Topic: 7 - Neuromuscular disorders Baff (B cell activating factor) can be the clinical marker in myasthenia gravis W. Sakaia, S. Nakaneb, T. Naritac, M. Motomurac, H. Matsuoa. aDepartment of Neurology, Nagasaki Kawatana Medical Center, Higashisonogi, Japan; b Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; cDepartment of Clinical Neuroscience and Neurology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Background: Myasthenia gravis (MG) is an antibody mediated disease in which the target autoantigen is the acetylcholine receptor (AChR) at the postsynaptic membrane of the neuromuscular junction. B cell activating factor (BAFF) is the potent B cell survival factor and is necessary for peripheral B cell differentiation and maturation. Excess BAFF promotes the survival and growth of autoreactive B cells. The previous studies have shown that serum BAFF levels in patients with MG are higher than in control subjects. BAFF may play an important role in the pathogenesis of MG. Objective: To compare serum BAFF levels in patients with AChR antibody positive MG (AChR MG) and muscle specific kinase antibody positive MG (MuSK MG). Patients and methods: We retrospectively analyzed 14 ocular AChR MG, 31 generalized AChR MG and 25 MuSK MG. We compared the serum BAFF levels with the clinical characteristics among 3 groups. Results: The serum BAFF levels in generalized AChR MG (1559.6 ± 108.6 pg/mL) were significantly higher than in MuSK MG (568.1 ± 36.3 pg/mL) and ocular AChR MG (598.1 ± 65.9 pg/mL). There was a correlation between the serum BAFF levels and disease severity in AChR MG. The serum BAFF levels of the generalized AChR MG with thymic abnormalities (1536.4 ± 728.8 pg/mL) were statistically higher than the ocular AChR MG. Conclusion: The serum BAFF levels are increased in patients with generalized AChR MG compaired to MuSK MG and ocular AChR MG. doi:10.1016/j.jns.2013.07.1536
Abstract - WCN 2013 No: 643 Topic: 7 - Neuromuscular disorders Autosomal recessive limb girdle muscular dystrophy: Prospective study and characterisation of 280 cases by immunohistochemistry and immunoblotting A. Nalini. Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India Background: ARLGMD is a common disorder in Southern India due to high consanguinity. Objective: To study pattern of ARLGMD in India. Materials and methods: Prospective study of 300 cases seen between February 2010 and October 2012. All suspected cases of ARLGMD