Biotransformation and elimination of digoxin with normal and minimal renal function

Abstract

Six subjects with normal renal jimction (NRF) and 6 patients with minimal renal function (MRF) on 3 times weekly hemodialysis received 150 jJ-Ci :lH-digoxin-120' orally. Serial urine collections were made for jive days or more. Digoxin and metabolites were separated using diethylaminoethyl Sephadex LH-20 column chromatography. Mean cumulative percentages of the ingested radioactivity excreted over jive days in NRF and MRF groups were: digoxin, 54.5% and 14.7%; bis-digilOxoside of digoxigenin, 2.0% and 0.50%; mono-digitoxoside, 0.8% and 0.19%; digoxigenin, 0.25% and 0.03%; and dihydrodigoxin, 0.3% and 0.03%. Haif~lives based on the mean rates of disappearance from urine comparing NRF and MRF groups were: for digoxin, 40 hr and 120 hr; for bis-digitoxoside, 11.5 hr and 46 hr;for mono-digitoxoside, 8.5 hr and 12 hr; for digoxigenin, 2 hr and 7.5 hr; and for dihydrodigoxin, 1.2 hr and 7.0 hr. Considering the relationships of the jive-day cumulative excretion and half-lives of digoxin and metabolites in the NRF and MRF groups, it appears unlikely that there is a major alteration in the biotransformation of digoxin in advanced renal failure It'hen There appears to be a shijt from renal to slower hiliary excretion.

Influence of gastric pH on digoxin biotransformation

“…18 Also, the rate of disappearance of digoxigenin from blood appears to be more rapid than digoxin, as the half-life has been reported as 3 2 and 2 hr 13 compared with 1.3 to 1.7 days for digoxin in those with normal renal function." 5, 13 Probably of equal significance is our finding (to be reported) that the mean methylene chloride extractable radioactivity in urine collected 0 to 5 hr after administration of 3H-digoxin-12a with pentagastrin was 46%, and 85% when administered with saline, The inotropic effect of the polar metabolites unextractable with methylene chloride could be less than that of digoxin.…”

Influence of SLCO1B3 Gene Polymorphism on the Pharmacokinetics of Digoxin in Terminal Renal Failure

“…However, the elimination half life of DX in patients with end-stage renal failure is reported to be more than 100 hours, 20) so that the differences in the DX concentrations at 62 and 72 hours after dosing is estimated to be less than 6.7%. Therefore, it is unlikely that the sampling time have significantly affected the C/D ratio in this study.…”

Metabolism of digoxin after oral and intrajejunal administration.

“…(Herrmann & Repke, 1969;Lindenbaum et al, 1981a). It can also be argued that not only the distal absorption but also individual factors may be responsible for the inactivation since the recovery of dihydrodigoxin differs greatly in previous investigations (Peters et al, 1978;Gault et al, 1979;Lindenbaum et al, 1981a, b;Magnusson et al, 1982b).…”

“…An explanation of the low production of dihydrodigoxin in the present study could be that the infusion of the glycoside was too proximal to allow exposition of the drug to bacteria possibly responsible for the metabolic process (Herrmann & Repke, 1969;Lindenbaum et al, 1981a). It can also be argued that not only the distal absorption but also individual factors may be responsible for the inactivation since the recovery of dihydrodigoxin differs greatly in previous investigations (Peters et al, 1978;Gault et al, 1979;Lindenbaum et al, 1981a, b;Magnusson et al, 1982b).…”