Plasma concentrations of digoxin in patients under intensive care conditions and in patients undergoing anesthesia and operation (author' transl)

Abstract

Pharmacokinetic behavior of digoxin or beta-acetyldigoxin was examined in 66 patients (27 patiets under intensive care conditions, partially with controlled breathing, 22 patients undergoing extirpation of the uterus and 17 patients treated with radium or chemotherapeutics; 19 males and 47 females) by determining plasma concentrations of digoxin (PDC). After intravenous and oral application with a maintenance dose of 0.20--0.50 mg/day blood was taken daily during a 2 to 3 week period, resulting in 510 determinations. 24 hours after the first application of 0.50 mg digoxin i.v. the mean values of PDC amounted to 0.62 +/- 0.08 ng/ml. After 0.40 or 0.25 mg digoxin per day i.v. therapeutical concentrations could be observed at the third vs fifth day. An equilibrium of PDC was reached on the 6th day after starting digitalization using maintenance doses. Intravenous application of 0.25, 0.40 or 0.50 mg digoxin per day resulted in a mean steady state of 0.68 +/- 0.37, 0.86 +/- 0.33 or 1.27 +/- 0.49 ng/ml PDC, respectively. The results were significantly different (p less than 0.01--0.001). Serial measurements indicated a great variation of PDC. In patients without renal failure the intraindividual variation of the plasma concentrations was maximal 37.4% referring to the mean steady state, interindividual 37.1% and the evaluation of the inter- and intraindividual differences amounted to 54.1%. After oral administration of digoxin (maintenance dose: 0.50 mg/day) or beta-acetyldigoxin (maintenance doses: 0.20--0.40 mg/day) differences in PDC of 38.3% and 29.7% were obtained. Body weight, age and serum creatinine concentration were partly responsible for the variance of PDC. Multiple linear regression between stead state PDC and dose, age, body weight and serum creatinine concentration revealed 62.1% of the variance of the PDC after intravenous administration of digoxin. After oral administration of beta-acetyldigoxin 39.9% were obtained. Thus, 40% of the variance were caused by differences in distribution and elimination of digoxin after i.v. application. After oral application additional 20% of the variance could be attributed to resorption and possible disturbances.