氨己烯酸的临床药理学
Clinical pharmacology of vigabatrin.
作者信息
Schechter P J
机构信息
Merrell Dow Research Institute, Strasbourg, France.
出版信息
Br J Clin Pharmacol. 1989;27 Suppl 1(Suppl 1):19S-22S. doi: 10.1111/j.1365-2125.1989.tb03456.x.
Abstract
- Upon oral administration vigabatrin is rapidly absorbed. Plasma elimination half-life ranges between 5 and 7 h in normal volunteers. Vigabatrin is eliminated primarily via the kidneys with about 65% of the administered dose found unchanged in the urine within 24 h. Kinetics are dose-linear within the range of usual therapeutic doses. 2. At therapeutic doses in man vigabatrin produces dose-related increases in CSF concentrations of free and total GABA, homocarnosine (the GABA-histidine dipeptide) and beta-alanine. These biochemical changes are consistent with an inhibition of GABA-transaminase activity in brain. 3. Thus, with systemic availability upon oral administration and biochemical activity in the CNS, the prerequisites for potential uses of vigabatrin in neurological disorders have been demonstrated in clinical pharmacological studies.
摘要
- 口服后，vigabatrin迅速被吸收。正常志愿者的血浆消除半衰期在5至7小时之间。Vigabatrin主要通过肾脏消除，给药剂量的约65%在24小时内以原形在尿液中被发现。在常用治疗剂量范围内，动力学呈剂量线性。2. 在人体治疗剂量下，vigabatrin使脑脊液中游离和总GABA、高肌肽（GABA-组氨酸二肽）和β-丙氨酸的浓度呈剂量相关增加。这些生化变化与脑中GABA转氨酶活性的抑制一致。3. 因此，凭借口服给药后的全身可用性和中枢神经系统中的生化活性，vigabatrin在神经疾病中潜在用途的前提条件已在临床药理学研究中得到证实。
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