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Biomedical subjects

G C Storey

Publications and source records attributed to G C Storey.

17 recordsLinked to original sources
PubMed1985

Use of amiodarone during pregnancy.

Two cases are reported in which amiodarone was administered during pregnancy for longer periods than has been reported previously. Limited placental transfer of amiodarone and its desethyl metabolite was observed in both cases. A normal child resulted from each pregnancy despite, in one case, amiodarone therapy throughout the entire pregnancy. However, caution is urged in the use of amiodarone during pregnancy in view of the limited data available.

Adult↗
PubMed1985

Amiodarone and its desethyl metabolite: tissue distribution and morphologic changes during long-term therapy.

The pharmacokinetic characteristics of amiodarone suggest extensive tissue deposition. We confirmed this by measuring tissue concentrations of the drug and of its major metabolite, desethylamiodarone, in human tissues. These were obtained at autopsy (n = 9), surgery (n = 7), or biopsy (n = 2) from 18 patients who had been treated with amiodarone for varying periods of time. High concentrations of amiodarone were found in fat (316 mg/kg wet weight in autopsy specimens, 344 mg/kg wet weight in biopsy specimens). Amiodarone and desethylamiodarone concentrations (mg/kg wet weight, autopsy samples) were also high in liver (391 and 2354), lung (198 and 952), adrenal gland (137 and 437), testis (89 and 470), and lymph node (83 and 316). We also found high concentrations of amiodarone (306 mg/kg wet weight) and desethylamiodarone (943 mg/kg wet weight) in abnormally pigmented ("blue") skin from patients with amiodarone-induced skin pigmentation. These values were 10-fold higher than those in unpigmented skin from the same patients. These high concentrations were associated with lysosomal inclusion bodies in dermal macrophages in the pigmented skin. The inclusion bodies were intrinsically electron dense and were shown to contain iodine by energy dispersive x-ray microanalysis. Lysosomal inclusion bodies shown by electron microscopy to be multilamellar were seen in other tissues. These tissues included terminal nerve fibers in pigmented skin, pulmonary macrophages, blood neutrophils, and hepatocytes and Kupffer cells. These characteristic ultrastructural findings occur in both genetic lipidoses and lipidoses induced by other drugs, e.g., perhexiline. We conclude that during therapy with amiodarone, widespread deposition of amiodarone and desethylamiodarone occurs. This leads to ultrastructural changes typical of a lipidosis. These changes are seen clearly in tissues associated with the unwanted effects of amiodarone, e.g., skin, liver and lung.

Adolescent↗
PubMed1984

Neuropathy and fatal hepatitis in a patient receiving amiodarone.

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.

Aged↗
PubMed1984

The pathogenesis of amiodarone-induced pigmentation and photosensitivity.

A new method has been used to measure tissue levels of amiodarone and its major metabolite desethylamiodarone. Amiodarone-pigmented skin has a drug and metabolite concentration ten times that of non-pigmented skin. Iodine-rich amiodarone and its metabolite have been detected in secondary lysosomes by energy dispersive analysis of X-rays. Amiodarone induces a phototoxic reaction with an action spectrum in both the UV-B and UV-A wavelengths.

Adult↗
PubMed1983

Amiodarone pharmacokinetics.

The single-dose pharmacokinetics of amiodarone have been studied in volunteer subjects given 400 mg doses by the intravenous and oral routes. The data show the compound to have a very large volume of distribution, a low total clearance, and a long and variable terminal elimination half-life. In patients the terminal elimination half-life was on the order of 40 days, with a more rapid phase of elimination in the first few days following the withdrawal of therapy. The terminal elimination half-life of desethylamiodarone was longer than that of the parent compound. High concentrations of amiodarone and its desethyl metabolite were found in tissue samples, with fat forming a potentially large tissue reservoir of the drug.

Adipose Tissue↗
PubMed1983

High-performance liquid chromatographic measurement of amiodarone and desethylamiodarone in small tissue samples after enzymatic digestion.

A method is described for the measurement of amiodarone and desethylamiodarone in small tissue samples. With the exception of fat, for which lipase is used, the tissues are digested with a proteolytic enzyme. After the addition of an internal standard the analytes are extracted from the homogeneous digest into an organic solvent and measured by high-performance liquid chromatography (HPLC) with UV detection at 240 nm. The method shows good reproducibility using tissue samples as small as 20 mg and suggests extensive accumulation of both compounds in some tissues, with particularly high concentrations in tissues associated with adverse effects of the drug.

Adipose Tissue↗
PubMed1983

Renal elimination of amiodarone and its desethyl metabolite.

Two patients in chronic renal failure receiving amiodarone for the treatment of refractory arrhythmias were commenced on dialysis, in one case, intermittent peritoneal dialysis, in the other, haemodialysis. Plasma concentrations of amiodarone and its desethyl metabolite were consistent with the dose received, whilst neither compound was recovered in the dialysate. In these patients and in 10 additional patients with normal renal function taking amiodarone, only negligible amounts of either compound were detected in urine. These findings suggest that amiodarone may be a suitable antiarrhythmic agent for use in patients with chronic renal failure.

Amiodarone↗
PubMed1982

High-performance liquid chromatographic measurement of amiodarone and its desethyl metabolite: methodology and preliminary observations.

A high-performance liquid chromatographic technique is described for the measurement of amiodarone and its desethyl metabolite in plasma. Preliminary observations are presented on the concentrations of metabolite found during the early stages of chronic amiodarone therapy. A case history is outlined in which noncompliance during treatment with amiodarone was confirmed by measurement of the ratio of desethylamiodarone to amiodarone concentrations.

Amiodarone↗
PubMed1982

Identification and measurement of desethylamiodarone in blood plasma specimens from amiodarone-treated patients.

Desethylamiodarone has been identified as the principal lipophilic metabolite of amiodarone present in plasma specimens from amiodarone-treated patients. This structure has been confirmed by probe-injection mass spectrometry of column effluent fractions and comparison with the authentic compound using both chromatographic and mass spectrometric techniques. Although there is no information available as to the pharmacological activity of desethylamiodarone in man, the plasma concentrations of this metabolite attained during chronic amiodarone therapy are similar to those of the parent compound (0.1-4 mg litre-1).

Amiodarone↗
PubMed1980

Rapid high-performance liquid chromatographic method for the measurement of amiodarone in blood plasma or serum at the concentrations attained during therapy.

A simple high-performance liquid chromatographic method has been developed for the measurement of the antiarrhythmic drug amiodarone in small (200 microliter) volumes of plasma or serum. After addition of 2 mole/l phosphate solution, pH 4.5 (20 microliter), containing the internal standard, the sample is vortex-mixed with diisopropyl ether (200 microliter) for 30 sec. A portion (100 microliter) of the resulting extract is analysed on a microparticulate (5 micron) silica column using methanol-diethyl ether (85:15) containing perchloric acid (0.02% v/v) as the mobile phase, and the absorption of the column effluent is monitored at 240 nm. No endogenous sources of interference have been observed, and interference from other drugs is minimal. The procedure is rapid, an analysis in duplicate taking less than 15 min to complete. The limit of sensitivity of the assay is 0.05 mg/l, and the concentrations of amiodarone measured in plasma samples from patients under treatment with this compound ranged from 0.15 to 4.5 mg/l.

Amiodarone↗