Elizabeth B. Solow

Plasma and red blood cell concentrations of amiodarone during chronic therapy

Amiodarone and a metabolite, desethylamiodarone, were measured in plasma of 55 patients and in both plasma and red blood cell (RBC) in 28 patients who received chronic amiodarone treatment. The assay for amiodarone and desethylamiodarone was performed by high-pressure liquid chromatography. During chronic treatment, median plasma concentration of amiodarone was 2.80 micrograms/ml and desethylamiodarone was 2.20 micrograms/ml. In matched samples, plasma amiodarone concentration exceeded RBC amiodarone concentration (p less than 0.001) and the RBC-to-plasma concentration ratio averaged 0.31. The plasma desethylamiodarone concentration was not significantly different from its RBC concentration, and the RBC-to-plasma concentration ratio averaged 1.29. There was a linear correlation between plasma concentrations of amiodarone and desethylamiodarone (r = 0.82) and between RBC concentrations of drug and metabolite (r = 0.71). Drug or metabolite concentrations in plasma and RBCs correlated directly with daily dosage of amiodarone. Adverse side effects during chronic amiodarone therapy were related most strongly to RBC drug and metabolite concentrations. The group with adverse side effects had a significantly higher RBC concentration of amiodarone, 150 vs 0.75 micrograms/ml (p less than 0.001), than did patients free of adverse effects. After dosage reduction, side effects abated and plasma and RBC concentrations of drug and metabolite decreased. These data indicate that there is an expected range of amiodarone and desethylamiodarone concentrations during chronic treatment and that adverse side effects correlate best with RBC concentrations of drug and metabolite. Red cell concentrations may reflect the amount of unbound, free amiodarone and desethylamiodarone in plasma.

The simultaneous determination of multiple anticonvulsant drug levels by gas-liquid chromatography. Method and clinical application.

The clinical usefulness of blood level determinations of antiepileptic drugs has been emphasized in a recent review by Rose et al.’ The technique of gas-liquid chromatography (GLC) has made possible rapid and accurate determination of serum levels without interference between drugs as in older ultraviolet methods.’-’ By a modification of the GLC method described by MacGee,6 it has been possible to determine simultaneously several anticonvulsant drug levels and to assay quantitatively as many as ten different compounds from a single extraction of serum. Results are available promptly, often the same day, so that drug dosage may be adjusted at the time the patient is seen or shortly afterward. Questions of intoxication are resolved promptly. The control of seizures is expedited by more rapidly reaching the therapeutic range of a drug, and the risk of overdosage is reduced. This report will attempt to indicate how experience with over 1,000 determinations of serum anticonvulsant levels has favorably influenced the management of epilepsy. A brief description of the GLC method used will be presented; for further details MacGee’s original paper should be consulted.

The determination of ethosuximide in serum by gas chromatography preliminary results of clinical application

Abstract A rapid gas-chromatographic method for the determination of ethosuximide in serum is reported. Clinical application has confirmed the reliability of the method.

Free fatty acid response to insulin and glucose stimulation in schizophrenic, autistic, and emotionally disturbed children

Three related studies of plasma free fatty acid metabolism involving 15 autistic and schizophrenic, 14 emotionally disturbed, and 49 normal children are reported and discussed. In the first, baseline FFA levels from 1 to 4 days showed significantly greater FFA variability in psychotic than in other children. In the second, contrary to paradoxical response in some adult schizophrenics, FFA lowered significantly and normally after intravenous insulin injection in 4 autistic children. In the third, involving glucose ingestion by 11 psychotic, 14 emotionally disturbed, and 13 normal children on high carbohydrate diets, subsequent FFA and glucose determinations at 45 minutes and 2 hours revealed no differences. Mean FFA levels were higher in the psychotic group. It is suggested that a possible reason for FFA variability in psychotic children may be a deficiency in the regulatory feedback mechanism at a neurogenic or cellular level.

Thrombosis During the Healing Phase

Twenty dogs were treated with either acetylsalicylic acid or a lactose placebo for 5.5 ± 2.3 days before surgical or chemical injury to the carotid and femoral arteries and for the following 34.5 days. Only the laboratory diener had knowledge of the random table used to select type of treatment until after all determinations had been completed. Following sacrifice the arteries were classified for the presence of intimal proliferation, defects in the internal elastica, presence of organized thrombi and the percentage of recanalization, and the presence of fresh thrombi and the percentage of occlusion. Thrombi were present in 8% of the arteries of dogs treated with acetylsalicylic acid and in 36% of those treated with placebo. This difference is significant (P<0.01). The degree of intimal proliferation and defects in the internal elastica were not significantly different between the two groups. We conclude that in dogs acetylsalicylic acid therapy during the healing phase following arterial injury protects against thrombosis and does not retard the healing process.