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Biomedical subjects

J K Penry

Publications and source records attributed to J K Penry.

At least 19 recordsLinked to original sources
PubMed1992

Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients.

The relationship between serum concentration and dose of valproic acid (VPA) is reported to be variable and inconsistent. However, studies evaluating this relationship have included individuals of varying ages and patients receiving potentially interacting medications. In this study, the relationship between VPA serum concentration and dose was evaluated in a homogeneous patient population. Medical records of 60 adult outpatients with epilepsy receiving VPA monotherapy were examined retrospectively for VPA dose (milligrams per kilogram) and corresponding serum VPA concentrations. A significant linear correlation was found in the relationship between VPA dose and serum concentration among all patients (r = 0.63; p less than 0.01). However, considerable interindividual variability in this ratio was demonstrated [coefficient of variation (CV) = 28.9%], and the ratio was significantly dependent on VPA dose. In three selected individual patients, a significant linear correlation was also demonstrated in the VPA serum concentration:dose relationship over time (r = 0.91, 0.94, 0.96; p less than 0.05 for all three patients) with substantially less variability (CV = 10.2-14.6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance. Further study is required to evaluate the utility of the serum concentration:dose ratio in monitoring VPA therapy.

Adult↗
PubMed1992

Therapeutic bioequivalency study of brand name versus generic carbamazepine.

We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency.

Adolescent↗
PubMed1979

Plasma concentrations of phensuximide, methsuximide, and their metabolites in relation to clinical efficacy.

The clinical efficacy of phensuximide and methsuximide was studied in relation to plasma concentrations of these compounds and their desmethyl metabolites. Single- and chronic-dose studies of each drug were carried out in five patients with intractable seizures. Patients were evaluated before and during treatment by 6-hour simultaneous video and telemetered electroencephalographic recordings to characterize the seizure type and by daily determinations of plasma antiepileptic drug concentrations. Phensuximide had a mean half-life of 7.8 hours and accumulated to an average fasting level of only 5.7 micrograms per milliliter. Desmethylphensuximide averaged only 1.7 micrograms per milliliter with a similar half-life. Methsuximide had an even shorter half-life, averaging 1.4 hours, but its desmethyl metabolite had a mean half-life of 38 hours and therefore accumulated to levels in excess of 40 micrograms per milliliter. The addition of phensuximide to their regimens benefited none of the patients, but two had an excellent response to methsuximide. The failure of phensuximide and its desmethyl metabolite to accumulate to reasonable levels is the likely explanation for the relatively weak antiepileptic effect of phensuximide as compared with methsuximide.

Drug Evaluation↗
PubMed1979

The use of antiepileptic drugs.

The use of antiepileptic drugs has become increasingly effective through several factors: new techniques that allow better diagnosis of the seizure disorder and its underlying cause; the development of new medications and increased knowledge of old ones; and the widespread use of antiepileptic drug-level determinations. The choice of a drug depends heavily on an accurate diagnosis of seizure type, which may determine the response to the medication. Because of better diagnostic criteria and intensive monitoring procedures, the correct seizure disorder can be more easily diagnosed and, therefore, the proper medication selected. Minimal efficacious and toxic blood concentrations have now been identified for most antiepileptic drugs. Several, including primidone, carbamazepine, methsuximide, and mephenytoin, have pharmacologically active metabolites that affect both the toxicity and efficacy of the prescribed drug and can now be measured in the plasma. The most effective use of the antiepileptic drugs depends on a combination of reliable blood level measurements, clinical observation, and knowledge of their pharmacokinetics and biotransformation.

Anticonvulsants↗
PubMed1978

Effects of ethanol, caffeine, and placebo on the auditory evoked response.

A previous paper (Wolpaw and Penry 1975) described separation of the 75-250 msec portion of the AER into N1P2, a product of large areas of cortex, and the T complex, probably a product of secondary auditory cortex. With monaural stimulation, the T complex is larger and earlier on the side contralateral to stimulation and on the right side. Thirty-one normal adults received 3 oz. of ethanol, 300 mg of caffeine, or placebo. Monaural AERs were recorded before intake in all cases, 1 and 4 h after ethanol and 80 min after caffeine or placebo. Blood levels of ethanol and caffeine were measured. Placebo produced mild (20%) decreases in N1P2 amplitude. Caffeine did not decrease N1P2 amplitude. It did produce a statistically significant 2% decrease in Ta peak latency. Ethanol reduced N1P2 amplitude markedly at 1 h and mildly at 4 h. Placebo did not affect hemispheric differences. Caffeine significantly increased the Ta peak ipsilateral vs. contralateral latency difference in 3 of 7 individuals. Ethanol significantly increased it in 3 of 6 subjects at 1 h and in 7 of 10 at 4 h, primarily by increasing ipsilateral latencies.

Adult↗
PubMed1978

Active noncompliance as a cause of uncontrolled seizures.

A 26-year-old woman with intractable seizures and fluctuating plasma phenytoin concentrations is described. Noncompliance with prescribed drug regimens was suspected. Phenytoin was first given as a capsule and then as an elixir. Ingestion of the capsule was monitored, and active non-compliance was proved and admitted by the patient. The causes of inadequate plasma phenytoin concentrations are few and can be determined either by specific laboratory methods or by changing the form of the drug.

Adult↗
PubMed1978

[Development of tolerance of phenobarbital after administration over several days (author's transl)].

In mice daily testing by maximal electroshock (MES) and pentylenetetrazole infusion (PTZ) 2 h after an i.p. injection of 25 mg/kg penobarbital (PB) was performed on days 1, 2, 4 through 8. The first twitch was delayed as compared to NaCl controls (50.4 +/- 4.8 s; 36.6 +/- 3.6 s; n = 53) on day 2, 4, 6 through 8. There was no tolerance of the PTZ induced tonic extension with Pb-treatment. In contrast, MES-tested mice developed tolerance, at day 5 the number of protected animals fell to about 50%. In view of the constant phenobarbital levels in plasma, a functional tolerance was assumed. The development of tolerance seemed to be connected with the spread of the discharge but not with discharge of the neurones themselves since it was observed only with MES but not wih PTZ-testing.

Animals↗
PubMed1977

Hemispheric differences in the auditory evoked response.

The separation of the 80-250 msec portion of the AER to click stimulation into N1P2, produced by large areas of cortex, and the T complex, probably produced by secondary auditory cortex, was recently described (Wolpaw and Penry 1975). The present study investigated the ipsilateral vs. contralateral and right vs. left hemispheric differences in N1P2 and T complex latencies and amplitudes. One msec clicks at 60 dB above threshold were presented at 4.7 sec intervals monaurally to 32 normal adults and binaurally to 13 of the 32. AERs were recorded from vertex and temporal referred to a balanced non-cephalic reference electrode. For monaural stimulation, N1P2 and T complex amplitudes were significantly greater and T complex latency was significantly less over the contralateral and right hemispheres. The ipsilateral vs. contralateral and right vs. left hemispheric amplitude differences were significanlty greater for the T complex than for N1P2. Binaural results, which provided in additional measure of right vs. left hemispheric differences, were in agreement with the monaural findings. The results are consistent with neurophysiologic and behavioral findings in regard to ipsilateral vs. contralateral and right vs. left hemispheric differences and support the hypothesis that the T complex is produced by secondary auditory cortex.

Adult↗
PubMed1977

Diagnostic and therapeutic reevaluation of patients with intractable epilepsy.

Intensive monitoring techniques were used to improve seizure diagnosis and control in 23 patients with intractable epilepsy: (1) Video recording of clinical seizures and the ictal EEG, (2) long-term telemetered EEG recordings, and (3) frequent determination of plasma antiepileptic drug concentrations. Patients were monitored in the hospital for an average of 8 weeks and after discharge were followed for an average of 8 months. At follow-up, 70 percent of the patients continued to have improved seizure control as compared with baseline studies, 83 percent had decreased toxicity, and about half had made gains in social adjustment. Use of the techniques described can make a significant contribution to patients previously considered intractable to therapy.

Adolescent↗
PubMed1976

Interlaboratory variability in determination of plasma antiepileptic drug concentrations.

The usefulness of plasma antiepileptic drug concentrations in treatment of epilepsy has been established, and many laboratories provide this service. A "blind" survey utilizing pooled patient plasma samples was conducted among 197 laboratories in the United States and Canada to establish the interlaboratory reproducibility. Three "patient specimens" containing different amounts of phenobarbital, phenytoin (diphenylhydantoin), primidone, and ethosuximide were employed; 112 laboratories reported results within five weeks. The average cost for analyzing four drugs in a single sample was $43.27. Half of the laboratories reported results outside +/- 1 standard deviation of the mean of five reference laboratories. Wide interlaboratory variability must be considered by the practicing physician. Until certified antiepileptic drug standards in a biologic matrix are available from the National Bureau of Standards, a volunteer quality control program among laboratories is needed.

Anticonvulsants↗
PubMed1976

Computer recognition of generalized spike-wave discharges.

Twelve 12h daytime telemetered EEGs were read for generalized spike-wave (S-W) bursts by a computer and independently by three experienced electroencephalographers. The computer system was a hybrid of analog devices (tape-recorder, voltage summator, and high-pass filters) and a multipurpose laboratory digital device (PDP-12). The computer was programmed to identify only the location on the record and the duration of the generalized S-W paroxysms. From 1,462 discharges identified by both the readers and the computer, a consensus list of 609 was derived by selecting only those bursts identified by all three readers. The computer recognized 516 (85%) of those bursts on the consensus list; the computer's accuracy, as compared with the consensus, rose to 92% when portions of the EEG containing sleep were discounted. The computer also recognized as generalized S-W paroxysms 15 high-voltage transients, which none of the three readers selected. Ten of these, however, occurred during sleep. When the computer results were added to those of the three readers to permit a four-way inter-reader comparison, the computer was found to have had about as many isolated decisions as any of the three readers. In the number of bursts recognized, the computer tended to be about as conservative as the reader under whose guidance it was originally programmed. The computer's accuracy in measuring burst duration was not evaluated statistically.

Computers, Hybrid↗