Benassi E, Besio G, Bo G P, Cocito L, Maffini M, Mainardi P, Morselli P L, Loeb C
Neurological Clinic, University of Genoa, Italy.
Int J Clin Pharmacol Res. 1988;8(5):353-61.
Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.
根据开放标签的长期设计，将γ-氨基丁酸受体激动剂丙戊酰胺（PGB）给予40名患有复杂部分性癫痫发作（有或无继发性全身性发作）且对卡马西平（CBZ）单药治疗反应不佳的成年患者。在两个月的卡马西平单药治疗参考基线期之后，进入为期两个月的“加用”期，在此期间，在不改变CBZ治疗方案的情况下添加递增剂量的丙戊酰胺；然后在15 - 60天内停用CBZ，并对患者进行长达12个月的丙戊酰胺治疗随访。27名患者完成了试验，但其中12名患者因停用CBZ后癫痫发作增加而不得不恢复使用CBZ + PGB联合治疗。在9名单用丙戊酰胺治疗的患者和6名接受CBZ + PGB联合治疗的患者中可观察到明确的治疗效果。发生了3例具有临床相关性的副作用，其中2例表现为明显焦虑，1例出现血清谷草转氨酶和谷丙转氨酶升高并有肝功能障碍的临床症状，停用丙戊酰胺后迅速恢复。总之，丙戊酰胺对约40%对现有抗癫痫药物反应不佳的患者的复杂部分性癫痫发作有效。尽管并非所有患者都能停用先前的抗癫痫药物，但丙戊酰胺单药治疗有时比CBZ单药治疗更有效，并且几名不得不恢复联合治疗的患者从丙戊酰胺的联合使用中获益。
