Abstract：
:Since the clinical data have been equivocal in regard to the effects of clonazepam (CZP) in focal-motor seizures, an alumina gel monkey model was used to evaluate quantitatively its efficacy with respect to this seizure category. The insolubility of CZP and its short biological half-life in monkey necessitated its evaluation in the model via constant-rate intravenous administration in a solution of polyethylene glycol 400 (PEG). Two groups of monkeys were given CZP in PEG (N = 6) or a PEG solution alone as a control compound (N = 5) for 6 weeks; these treatments were bordered at both ends by 3 weeks of treatment with saline only in order to establish a baseline. CZP was administered at a concentration sufficient to achieve a plasma level of 30 ng/ml in drug step I (3 weeks) and at least double that level in drug step II (3 weeks). As a solute for CZP, and when given by itself, PEG was always administered at a concentration of 35%. The results indicate that CZP is effective for focal-motor seizures and secondarily generalized tonic-clonic seizures, particularly when its concentration in plasma is higher than 60 ng/ml. Withdrawal seizures were evident on cessation of CZP administration. CZP appears to be a useful broad-spectrum anticonvulsant when managed carefully. An unexpected finding was the irreversibility of the pharmacological effect of PEG. Cessation of PEG administration significantly reduced seizure frequency in subsequent weeks to a level below the initial baseline level.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Lockard JS,Levy RH,Congdon WC,DuCharme LL,Salonen LDdoi
10.1111/j.1528-1157.1979.tb04852.xkeywords:
subject
Has Abstractpub_date
1979-12-01 00:00:00pages
683-95issue
6eissn
0013-9580issn
1528-1167journal_volume
20pub_type
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