Antiseizure drugs pharmacokinetics

The antiseizure drugs exhibit many similar pharmacokinetic properties—even those whose structural and chemical properties are quite diverse— because most have been selected for oral activity and all must enter the central nervous system. Although many of these compounds are only slightly soluble, absorption is usually good, with 80-100% of the dose reaching the circulation. Most antiseizure drugs (other than phenytoin and valproic acid) are not highly bound to plasma proteins. 

The pharmacokinetic properties of the benzodiazepines in part determine their clinical use. In general, the drugs are well absorbed, widely distributed, and extensively metabolized, with many active metabolites. The rate of distribution of benzodiazepines within the body is different from that of other antiseizure drugs. Diazepam and lorazepam in particular are rapidly and extensively distributed to the tissues, with volumes of distribution between 1 L/kg and 3 L/kg. The onset of action is very rapid. Total body clearances of the parent drug and its metabolites are low, corresponding to half-lives of 20-40 hours. 

PHARMACOKINETICS Gabapentin is absorbed after oral administration and excreted unchanged, mainly in the urine. Its tj 2> when used as monotherapy, is 4-6 hours. It has no known interactions with other antiseizure drugs. 

PHARMACOKINETICS Zonisamide is almost completely absorbed after oral administration, has a long tj, ( 63 hours), and is -40% bound to plasma protein. Approximately 85% of an oral dose is excreted in the urine, principally as unmetaboUzed zonisamide and a glucuronide of the CYP3A4 metabolite, sulfamoylacetyl phenol. Phenobarbital, phenytoin, and carbamazepine decrease the plasma concentration/dose ratio of zonisamide, whereas lamotrigine increases this ratio. Zonisamide has Uftle effect on the plasma concentrations of other antiseizure drugs. 

Describe the main pharmacokinetic features and adverse effects of major antiseizure drugs. 

Pharmacokinetics Antiseizure drugs are commonly used for long periods of time, and consideration of their pharmacokinetic properties is important for avoiding toxicity and drug interactions. For some of these drugs (eg, phenytoin), determination of plasma levels and... 

Which one of the following statements concerning the pharmacokinetics of antiseizure drugs is accurate ... 

Table 20.2. Mechanism(s) of Action and Pharmacokinetics for Antiseizure Drugs ...

Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiseizure drugs in pediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine, and felbamate. Clin Pharmacokinet 1995 29 341-369. 

As indicated earlier, the development of the newer antiseizure medications has advanced the strategy of using two drugs rather than a single agent. Because these newer drugs have relatively predictable pharmacokinetic and side-effect profiles, they can be added to traditional medications without excessive complications and risk to the patient.4,31 Combination therapy is therefore a more common approach to treating seizure disorders than it was in the past. 

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