On the absorption of proscillaridin A after single oral doses to normal and achlorhydric subjects.

Proscillaridin A was given in single oral doses (1.5-2.5 mg) to normal and achlorhydric subjects. Plasma activities of the glycoside were analysed by 86Rb-technique. The absorption pattern was similar in both groups. A marked first peak of proscillaridin activity was seen after about 30 min. After a first minimum, a second peak of activity was registered within 6-12 hrs. An estimate of the amount of active glycoside absorbed during the first 12 hrs after the administration was obtained by calculating the areas under the plasma activity curves (AUC). When corrected for differences in dose per kg body weight, the mean AUC in the achlorhydric group was about 60 per cent greater than in the normal group. The results suggest that proscillaridin is rapidly absorbed; gastric acidity seems to contribute to inter-individual differences in the bio-availability of the glycoside.

On the pharmacokinetics of proscillaridin A in man.

The plasma concentration of proscillaridin was measured by a modified 86Rb method during treatment with multiple doses of a commercial preparation of proscillaridin. Despite high doses, very low plasma levels were found, and there were only minute amounts of glycoside activity in urine and faeces. Administration of an enteric-coated proscillaridin preparation gave higher plasma levels, which raises the possibility of inactivation of the glycoside by acid gastric juice. The results suggest that proscillaridin has low biological availability when given orally, and that it is extensively metabolised in the body.

Cardiac arrhythmias, electrolytes, and digoxin concentration in plasma and urine in patients treated with digoxin.

Cardiac arrhythmias, digoxin concentration in plasma and urine, digoxin and creatine clearances, electrolytes in plasma and in erythrocytes, and subjective symptoms have been carefully studied for 5 consecutive days in 19 patients with definite or suspected digitalis intoxication. The digoxin treatment was discontinued during the observation period. Eleven controls without any signs of toxicity were similarly followed on unchanged maintenance dosage. All patients were independently classified as toxic or non-toxic from the follow-up of extended ECG recordings and subjective symptoms. In 9 definitely toxic patients a plasma digoxin concentration 3.1 plus or minus 0.7 ng/ml was found, as compared to 1.4 plus or minus 0.5 ng/ml for the 11 controls. In the suspect toxic group 1.5-3.9 ng/ml was found. The high digoxin level in the toxic group corresponds to a low digoxin clearance. In the toxic patients cardiac arrhythmias were related in most cases to a plasma digoxin level above 2.5 ng/ml and usually disappeared when the concentration had decreased below this. Suspect toxic patients, classified as probably non-toxic, and controls had with two exceptions plasma digoxin levels below 2 ng/ml. It is suggested that digitalis toxicity should be considered at a plasma digoxin concentration above 2 ng/ml. It must be stressed that this limit is not absolute and is affected by, among other things, a disturbance of intra- and extracellular electrolytes.

In vitro stability of proscillaridin A.

In an in vitro study, proscillardin A was found to be rapidly inactivated at low pH. More than 50 per cent of its activity, measured by 86Rb assay, was lost after incubation for 15 minutes at pH 1 and 37 degrees C. Compared with proscillaridin, the rate of inactivation of digoxin was lower in these experiments. The rapid inactivation of proscillaridin might be of clinical importance when treating patients with this glycoside.