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Fifteen patients with spontaneous systemic lupus erythematosus (SLE) have been phenotyped by determination of plasma isoniazid (INH) half-life. Seven patients had signs of renal insufficiency. Of the 15 patients, 13 were slow and only 2 rapid acetylators. No correlation was found between the plasma INH half-lives and the renal function. Thus, there is the same marked predominance of slow acetylators in patients with spontaneous SLE as in patients with the drug-induced SLE-like syndrome.

Haptoglobin catabolism has been studied in 17 subjects with the aid of 131I- and 125I-labelled haptoglobin. The catabolism has been found to be in the order of 10–20% of the i.v. pool per day—a catabolic rate significantly lower than that reported by previous investigators.

1 A specific gas-chromatographic method was developed for determination of N-acetylprocaine amide in plasma and urine, using 4-amino-N-(2-piperidinoethyl)benzamide as an internal standard. The investigation was performed in 50 cardiac patients who had reached steady-state plasma concentrations of procaine amide. 2 The plasma concentrations of the acetylated metabolite varied between 1.0 and 15.0 μg/ml and were thus of the same order of magnitude as those of the parent drug. Especially high plasma levels of the metabolite were seen in patients with poor kidney function. 3 The urinary excretion of the metabolite varied markedly between individuals and ranged between 6 and 52% of the administered daily dose. There was a clear tendency towards higher rates of acetylation of procaine amide in patients with short plasma half-lives of isoniazid, i.e. the phenotype rapid acetylators. Because of coexisting therapy with other drugs and impaired renal function in some patients studies are required in healthy human volunteers to ascertain whether the acetylation of procaine amide and isoniazid are mediated by the same enzyme system.

The concentrations of digoxin in plasma and urine samples obtained from three healthy male volunteers, who received 1.2 mg of labeled digoxin perorally and intravenously, were simultaneously measured by a commercially available radioimmunoassay (RIA) and by a combined column thin-layer chromatographic assay (CA). The CA method, previously shown to assay digoxin specifically, was also used to monitor the individual digoxin metabolites. The results of this investigation showed that digoxin was significantly metabolized, particularly after peroral administration. The lower level of sensitivity of the RIA in plasma was 0.4 ng/mL. There were highly significant positive linear correlations between the values of the following parameters of digoxin as obtained by the RIA and CA methods: the concentrations in plasma and urine, the AUCs, and the cumulatively excreted amounts in urine. The two assays did not give completely identical results either with plasma or urine; the slopes of the regression lines deviated from unity in a significant number of cases. However, there was no relationship between the magnitude of the slopes of the regression lines and the extent of metabolism. It was concluded that the commercially available RIA evaluated was specific for digoxin and that the presence of digoxin metabolites did not affect the determinations.

We studied the interference of the sample matrix on digoxin radioimmunoassays using four commercial kits. Plasma samples from non-digitalized patients of the following categories were assayed: uncomplicated essential hypertension treated with spironolactone, uremia, and acute myocardial infarction (AMI). Digoxin 2.50 nmol/L was added to all samples. Digoxin in plasma from patients on spironolactone was overestimated by two of the kits (means 2.77 and 2.68 nmol/L, respectively; p less than 0.01) and underestimated in samples from uremic patients by one kit (2.32 nmol/L; p less than 0.01). The digoxin content of AMI plasma was overestimated by one kit (2.62 nmol/L; p less than 0.05). Significant differences were found between radioimmunoassays when estimating digoxin concentration in the same category of patient and within individual methods used for different categories. Precision expressed as 95% confidence intervals ranged from 0.43 to 0.80 nmol/L for the kits. Thus, deviations in recorded digoxin concentrations from the true values found, but were of secondary importance because of the relatively low precision of the assays.

The acetylator phenotype of 35 healthy, drug-free volunteers and 21 patients with cardiac and/or renal disease has been assessed using oral sulphapyridine. Comparative evaluation of a simplified and a more selective method of sulphapyridine analysis was performed. Thirteen of the patients were also phenotyped by determination of plasma isoniazid half-life. 81% of the patients were slow acetylators, compared with only 51% of the volunteers. When phenotyping healthy, drug-free subjects the analytical procedure, involving a direct estimation of sulphapyridine in urine with the Bratton-Marshall procedure, was satisfactory. On the other hand, in patients receiving concomitant drug therapy the more selective analytical procedure was necessary in order to diminish the risk of methodological interference.

The acetylation of procaine amide has been studied by means of gas liquid chromatography in 33 healthy human volunteers. The acetylator phenotype was determined by measuring unchanged and acetylated sulphapyridine in urine. Slow acetylators of sulphapyridine excreted significantly less procaine amide in acetylated from in the urine than rapid acetylators (9 plus or minus 1% against 19 plus or minus 4%). Hence, it is suggested that the acetylation of procaine amide is subject to the same genetic polymorphism as that of isoniazid and some sulfonamides.

The reliability of the ankle jerk test (AJT) as an indicator of thyroid hypofunction has been studied in a health survey. A strong correlation was found between the AJT and the results of clinical scoring. The AJT could not be correlated to the serum FBI, cholesterol or the T3-resin uptake test. As the diagnosis of thyroid hypofunction remains primarily clinical, the AJT is suggested as the method of choice for screening purposes as compared to PBI, cholesterol and T3-resin uptake measurements.