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Biomedical subjects

C E Pippenger

Publications and source records attributed to C E Pippenger.

At least 55 records · Page 3Linked to original sources
PubMed1980

Effect of dietary protein and carbohydrate on theophylline metabolism in children.

Theophylline metabolism can be altered by a variety of abnormal physiologic states as well as by exogenous factors. Adult studies demonstrate a significant influence of dietary composition on theophylline biotransformation. To examine this effect of diet, 14 children with bronchial asthma were studied during long-term theophylline administration. Each patient was maintained for 12 days on three separate diets with varying proportions of protein and carbohydrate and with constant calories and fat. Results showed significant differences in drug half-life and metabolic clearance rate parameters. Compared to the normal diet, high protein diet markedly decreased the half-life, and high carbohydrate diet greatly prolonged it (P < .001). Multiple regression analysis demonstrated these differences to correlate only with the dietary alterations. Adverse reactions and blood chemistry abnormalities were not detected during any test period. These findings firmly establish that nutritional factors exert a significant influence on theophylline pharmacokinetics in children.

Adolescent↗
PubMed1978

Evaluation of EMIT methods for the determination of the five major antiepileptic drugs on an automated kinetic analyser.

We have evaluated the performance of enzyme-multipled immunoassay methods for the five major antiepileptic drugs on an automated system, the Perkin-Elmer Model KA-150 Kinetic Analyzer. The precision in the normal duplicate mode was found to be in the range of 6% to 10% for all five tests over a typical working day. All EMIT methods were compared to gas-liquid chromatographic procedures and, in addition, the phenytoin and phenobarbital assays were compared to a liquid-chromatographic method. The phenytoin assay was also compared to RIA and to a manual spectroscopic method. In general, most of the comparison studies resulted in acceptable correlation, although one gas chromatographic method did not correlate very well with the phenytoin and phenobarbital immunoassays.

Anticonvulsants↗
PubMed1977

Salivary levels of anticonvulsants: a practical approach to drug monitoring.

Phenobarbital, phenytoin, carbamazepine, primidone, and ethosuximide were measured in saliva and plasma obtained simultaneoulsy from 115 patients. A method to correct for the effect of salivary pH on phenobarbital concentration of saliva was developed. Salivary concentrations of these drugs were found to be equivalent to the plasma free drug and to correlate closely with the total plasma levels. Expressed as percent of total plasma drug, the salivary (S) and plasma free (P) concentrations were: phenytoin, S 11.1 +/- 2.0 percent (mean +/- SD), P 10.1 +/- 2.4 percent (r = 0.97); carbamazepine, S 26.0 +/- 2.4 percent, P 25.9 +/- 3.4 percent (r = 0.97); phenobarbital, S 43.1 +/- 5.2 percent, P 40.8 +/- 7.9 percent (r = 0.91); primidone, S 75.4 +/- 24.9 percent, P 66.4 +/- 8.8 percent (r = 0.76). Ethosuximide was not bound by plasma proteins, and its plasma and salivary levels were equal.

Anticonvulsants↗
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

The relation of anticonvulsant drug levels to complete seizure control.

This study was undertaken to determine the relationship of serum ACD levels to dosage in a group of patients who had been seizure free for at least two years. It demonstrated that some patients remain completely seizure free with DPH and/or phenobarbital serum concentrations which are well below the reported "optimal" therapeutic ranges. In addition, medicating patients with anti-convulsant drugs solely on the basis of mg/kg of body weight does not assure optimal ACD levels in any given patient. Certain patients can be maintained completely seizure free controlled with DPH and/or Pb levels of less than 10 micrograms/ml. There are several explanations for the medication concentrations observed in these patients: (1) patient noncompliance in ingestion of prescribed medication; (2) altered drug utilization; (3) a mild focus which is maintained under control with lower DPH levels than those necessary to control a more active focus; or (4) epilepsy in remission. Our observations emphasize the importance of individual regulation of medications for seizure control.

Adolescent↗
PubMed1976

The effects of lidocaine on the canine ECG and electrophysiologic properties of Purkinje fibers.

Effects of selected plasma lidocaine concentrations on the action potentials of isolated canine Purkinje fibers were studied with microelectrode techniques and a method for perfusing PF with the arterial blood of a normokalemic dog. Lidocaine was administered to the donor as an intravenous injection of 0.5 to 2.0 mg. per kilogram or as an intravenous infusion of 4 to 50 mug per kilogram per minute and plasma concentrations were determined by gas chromatography. At plasma lidocaine concentrations from 0.2 to 9.9 mug per milliliter no significant changes in donor arterial pressure, heart rate, or electrocardiographic P-R and QRS intervals occurred, and Purkinje fiber resting membrane potential was unchanged. Donor Q-T intervals were unchanged at lower lidocaine concentrations (up to 4.0 mug per milliliter) and decreased at higher levels (4.1 to 9.9 mug per milliliter). Purkinje fiber AP changes commenced in 2 to 3 minutes of lidocaine injection. At lower lidocaine levels AP amplitude, maximum slope of phase 0 depolarization (Vmax) AP duration, and effective refractory period decreased, membrane responsiveness was depressed, and automaticity of spontaneously firing Purkinje fibers decreased. These changes were accentuated at higher lidocaine concentrations. Conduction usually was unchanged or slowed at lower plasma lidocaine levels and slowed at higher concentrations. When ouabain-intoxicated preparations were studied, lidocaine exerted a depressant effect on the AP. These studies indicate that the mechanisms whereby therapeutic lidocaine concentrations may modify arrhythmias are not unlike those of other local anesthetics and include depression of Vmax, membrane responsiveness, and conduction.

Action Potentials↗
PubMed1976

Pharmacologic observations on the neonatal withdrawal syndrome.

The relationship between a maternal dose of methadone and the incidence and severity of neonatal signs of withdrawal, placental transfer of drug, and the relationship between maternal and neonatal plasma levels of methadone were studied in 30 mothers and their infants. Plasma levels of methadone were analyzed using a gas chromatographic method. Our studies demonstrate that the relationship between maternal dose of methadone and the incidence of neonatal withrawal symptoms was closely related to the last maternal dose of methadone. The ratio of neonatal to maternal plasma concentrations of methadone was 2.2:1. Neonatal withdrawal symptoms appear to be related to individual variation in maternal metabolism of the drug, placental transfer of methadone, and most importantly, to the individual variations in the rate of excretion of methadone as reflected in the neonatal plasma t 1/2. At plasma levels of methadone greater than or equal to 0.06 mug/ml, the symptomatic patients appeared to be protected from withdrawal. When the plasma concentration fell below this level, withdrawal symptoms began within 24 hours.

Female↗
PubMed1976

Effects of therapeutic concentrations of diphenylhydantoin on transmembrane potentials of normal and depressed Purkinje fibers.

Standard intracellular microelectrode techniques were used to study canine Purkinje fibers (PF) which had been superfused with blood or Tyrode's solution to determine the cardiac cellular electrophysiologic changes induced by antiarrhythmic concentrations of diphenylhydantoin (DPH). Some PF were normal whereas others were depressed by stretch, exposure to ouabain (125 mug/1) or superfusion with a solution in which all Na+ was replaced by tetraethylammonium. For normal fibers, therapeutic concentrations of DPH (DPH) induced slight decreases in action potential (AP) amplitude, maximum upstroke velocity of phase O (Vmax) and membrane responsiveness and somewhat greater decreases in AP duration. For fibers moderately depressed by ouabain or stretch, with reduced AP amplitude, maximum diastolic potential and Vmax, therapeutic [DPH] increased these variables. Fibers markedly depressed by Na-free solution or stretch developed slow response AP. The amplitude and Vmax of the AP were decreased by therapeutic [DPH]. Therapeutic [DPH] also suppressed automaticity and ouabain-induced delayed afterdepolarizations. Our studies suggest that the slight depression of normal PF AP characteristics induced by therapeutic [DPH] probably is of little significance with respect to antiarrhythmic effect. In contrast, both the improvement of AP characteristics of moderately depressed fibers and further depression of severely depressed fibers caused by [DPH] might modify arrhythmias. Effects of DPH on automaticity and delayed afterdepolarizations also would contribute to its antiarrhythmic effect.

Action Potentials↗
PubMed1975

Seizure activity and anticonvulsant drug concentration.

Current methods permit frequent, accurate serum anticonvulsant drug concentration measurements and continuous, 24-hour electroencephalographic recording with minimal environmental restriction. These techniques were used to perform longitudinal, 24-hour recordings of electroencephalographic paroxysmal activity and sleep-wake state concurrently with frequent measurements of serum anticonvulsant drug concentrations in two patients with poorly controlled convulsions. Drug administration was designed with the intent of producing high serum concentrations at times of maximum electroencephalographic paroxysmal activity. The suppression of clinical seizures coincided with decreased numbers of paroxysmal bursts in the electroencephalogram and increased serum anticonvulsant drug concentration.

Anticonvulsants↗