Digoxin intravenous infusion

Figure 10 Effect of repeated administration of rifampicin on the time profile of the plasma concentration of digoxin following intravenous and oral administration. Eight healthy male volunteers [age 29 5 years, body weight 84 9 kg (mean SD)] were included in the study. Plasma concentration (mean SD) time curves of digoxin given orally (1 mg) (A) and intravenous infusion over 30 minutes (1 mg) (B) before open circles) and during (filled circles, day 11) coadministration of rifampicin (600 mg, once daily orally for 16 days). Source From Ref. 372.

The thrombin inhibitor argatroban had no effect on the steady-state pharmacokinetics of oral digoxin 0.375 mg/day in 12 healthy volunteers the argatroban was given as an intravenous infusion of 2 micrograms/kg/minute on days 11-15 (236). 

In Equation 17.22, the body is considered as a single homogeneous pool of body fluids as described above for digoxin. For most drugs, however, two or three distinct pools of distribution space appear to exist. This condition results in a time-dependent decrease in the measurable blood or plasma concentration, which reflects distribution into other bod pools independent of the body s ability to eliminate the drug. Figure 17.3 describes mean serum IFN-a concentrations after a 40-min intravenous infusion as well as after intramuscular and subcutaneous injections of the same dose. Note the logarithmic biphasic nature of the mean plasma concentration-time curve after the intravenous infusion. This biphasic nature represents both the distribution and elimination processes. 

In several cases the special nature of a formulation will preclude dilution by an aqueous infusion fluid. Injectable products containing phenytoin, digoxin and diazepam may come into this category if they are formulated in a nonaqueous but water-miscible solvent (such as an alcohol-water mixture) or as a solubilised (e.g. micellar) preparation. Addition of the formulation to water may result in precipitation of the dmg, depending on the final concentration of the dmg and solvent. It has been suggested that precipitation of the relatively insoluble diazepam may account for the high (3.5%) incidence of thrombophlebitis which occurs when diazepam is given intravenously. 

Concentrated solutions of quinine may cause abscesses when injected intramuscularly or thrombophlebitis when infused intravenously. GI absorption of quinine can be delayed by antacids containing aluminum. Quinine and quinidine can elevate plasma levels of digoxin. Likewise, the alkaloid may raise plasma levels of warfarin. The action of quinine at neuromuscular junctions will enhance the effect of neuromuscular blocking agents and oppose the action of acetylcholinesterase inhibitors. Prochlorperazine can amplify quinine s cardiotoxicity, as can halo-fantrine. The clearance of quinine is decreased by cimetidine and increased by acidification of the urine and by rifampin. 

An experimental study in 8 patients with congestive heart failure found that when they were given either sodium nitroprusside hy infusion (7 to 425 micrograms/minute) or hydralazine hy intravenous injection (5 mg every 10 to 20 minutes to a total dose of 10 to 60 mg) the total renal digoxin clearance was increased by about 50% by both drugs and the serum digoxin levels were decreased by 20% by the nitroprusside and 11% by the hydralazine. ... 

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