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Biomedical subjects

P N Friel

Publications and source records attributed to P N Friel.

5 recordsLinked to original sources
PubMed1979

Single-dose pharmacokinetics and anticonvulsant efficacy of primidone in mice.

The pharmacokinetics and efficacy of the anticonvulsant primidone (PRM) and its active metabolites, phenobarbital (PB) and phenylethylmalonamide (PEMA), were studied after single-dose administration in mice. The half-life of PB is twice that of PRM and PEMA. The plasma/brain ratios provide evidence of poor penetration of PRM into brain. The results support our findings of negligible or absent PRM concentrations in the brains of patients on primidone therapy who were undergoing surgery for intractable epilepsy. The anticonvulsant properties of PRM, PB, and PEMA against maximal electroshock in mice were also studied with the use of the metabolic inhibitor SKF 525A. The half-life, potency, peak anticonvulsant effect, and effective dose curves of these compounds indicate that the anticonvulsant effect of short-term oral PRM administration in mice is from derived PB.

Animals↗
PubMed1979

Valproic acid-phenytoin interaction.

The interaction between valproic acid (VPA) and phenytoin (DPH) was examined during therapeutic monitoring in an epileptic outpatient population. Gas-liquid chromatographic methods were used to measure DPH and VPA concentrations. (1) In 12 patients on stable DPH regimens, the mean DPH level declined from 19.7 to 15.3 microgram/ml when VPA was added (p less than 0.001). (2) In 20 patients receiving DPH and VPA, the median free fraction was 15.8%, compared to 9.1% free DPH in 40 patients receiving DPH only or DPH and phenobarbital (p less than 0.001). (3) Addition of VPA to a stable DPH regimen may result in a transient increased risk of DPH toxicity, followed by restabilization at the original free DPH level.

Adult↗
PubMed1979

A methods comparison: clonazepam by gas chromatography-electron capture and gas chromatography-mass spectroscopy.

Clonazepam is an antiepileptic drug for which a number of analytical procedures have been presented, none of which have been subjected to comparison studies. We present two gas chromatographic (GC) methods involving distinct forms of detection for determining plasma or serum drug levels. Both methods involve simple extractions, common GC conditions, and routine data reduction. Both employ nitrazepam as an internal standard, require 1 ml of sample, and have a detection limit of 1 ng/ml. The two methods, GC-electron capture and GC-mass spectroscopy, are precise and accurate. Correlation of the two methods paired sample analysis gave a regression equation of y = 0.988x - 0.14 (n = 30, r = 0.971, p less than 0.001). We suggest that either method is a reasonable alternative for the clinical laboratory with the proper instrumentation.

Benzodiazepinones↗
PubMed1975

Human epileptic brain Na, K ATPase activity and phenytoin concentrations.

An abnormal flux of monovalent cations may be related to the epileptogenic process in man. One possible mechanism for deranged electrolyte metabolism in epileptic brain is an abnormality in sodium, potassium-dependent adenosine triphosphatase (Na, K ATPase). We found the activity of Na, K ATPase to be significantly less in epileptic human corfex than in nonepileptic cortex. Histological changes have been simultaneously evaluated in epileptic brain. A second membrane-bound enzyme, acetylcholinesterase (AChE), was also assayed as a marker for neuronal membranes and found not to correlate with the epileptogenicity of human brain. In addition, the concentrations of the anticonvulsant compound phenytoin have been determined in the serum and cerebral cortex of epileptic and nonepileptic patients. The ratio of phenytoin in cortex to serum concentration is significantly lower in epileptic patients than in nonepileptic controls.

Acetylcholinesterase↗