Pharmacokinetics Parameters of Diagoxin among Saudi Patients in Qassim Region, Saudi Arabia

Background: The pharmacodynamic effects of digoxin are susceptible to multiple factors, most notably, heart uptake of the digoxin dose and its concentration in the serum. Another important factor to mention is the renal function state of an individual. Objective: In this study, we aimed to develop a simple algorithm based on subsets of clinically relevant information, which will help to personalize digoxin based on pharmacokinetic (PK) approach, which can help on marketing the appropriate utilization of this medication. Method: This was a retrospective chart review and analysis of 48 patients who were admitted to the Drug and Poison Information Center in Buraidah, Saudi Arabia, between January 2016 and April 2019. All pharmacokinetic parameters were added according to the C-peaks and C-troughs. MONOLiX® was used for pharmacokinetic data analysis. Results: Twenty-seven (56%) were males, and twenty-one (44%) were females with an average age of 63.6 years across both genders. The mean volume of distribution was 496.6 litres with an average clearance of 6.6 L/h. For females, their average volume of distribution was slightly higher than that for males (526 litres compared to 473 liters). In addition, the clearance rate between both genders showed a 2.1 litre/hour discrepancy (7.8 L/h for females compared to 5.7 L/h for males). Conclusion: In order to individualize the digoxin dosage regimens, this model can be used to predict digoxin serum concentration. Further studies are needed to clarify the effects of nutritional status and co-administration of medications on digoxin pharmacokinetics.

Use of Digoxin Monitoring in a Hospital Setting as an Essential Tool in Optimizing Therapy

Objective To determine what triggers the use of digoxin therapeutic drug monitoring (TDM) that adheres to established indications and the change in digoxin dosage after the result of monitoring is obtained. Methods This prospective study included 86 patients admitted to 6 medicine wards and 2 intensive cardiac care unit wards in a tertiary-care center. Data on patients' demographics, drug therapy, serum chemistry values, indications for digoxin therapy, indications for ordering the drug assay, timing of the blood sample relative to administration of the last dose, and physicians' decisions after attaining serum digoxin concentrations were collected. Results Eighty-six digoxin assays were evaluated. Indications for the use of a digoxin assay were mostly routine without a clear indication (66%); in only 22% of the assays were orders considered clinically justified. Eleven patients had concentrations >2 ng/mL, but only 8 patients had digoxin intoxication. In only 31% of patients did the medical staff respond to the results. In only 21% of patients with subtherapeutic drug concentrations was there a change in digoxin dose. Conclusions Although there are clear indications for the use of digoxin TDM, physicians seem to routinely order these blood tests. The clinicians did not adequately use the digoxin concentration data to optimize therapy. The assistance of a clinical pharmacist or pharmacologist is warranted for use of the assays, to optimize digoxin therapy.

Erythromycin-Induced Digoxin Toxicity

The potential interaction between certain antibiotics and digoxin has been discussed in the literature; however, few cases of actual erythromycin-induced digoxin toxicity have been reported. We present a case in which an 86-year-old woman who was taking digoxin 0.25 mg/d developed probable digoxin toxicity after the administration of erythromycin for the treatment of otitis media and streptococcal pharyngitis. Her digoxin concentration increased from a trough of 1.9 to 5.1 nmol/L six days after the erythromycin was started. Digoxin was discontinued and restarted approximately six weeks later when the patient's atrial fibrillation and congestive heart failure recurred. Her digoxin dose at this time was 0.125 mg/d and resulted in steady-state concentrations of 1.2, 1.4, and 1.2 nmol/L over the next year. Erythromycin inhibition of Eubacterium lentum, which converts digoxin into digoxin-reduction products in the gut, is the proposed mechanism of this interaction.

The effect of inhibitors of endogenous opioid degradation, bacitracin, bestatin, captopril, and D-phenylalanine, on digoxin-induced arrhythmias in guinea pigs

The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 μg/kg i.v. bolus of digoxin followed by 500 μg∙kg−1∙h−1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p < 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p < 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 μg/kg bolus and 50 μg∙kg−1∙h−1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg∙kg−1∙h−1 i.v., was followed by 100 μg/kg digoxin i.v. every 15 min. Bacitracin significantly (p < 0.05) reduced the digoxin dose at the development of arrhythmias. This was reversed by naloxone, given as 2 mg/kg i.v. plus 10 mg∙kg−1∙h−1. Thus, these data indicate that inhibitors of degradation of some opioid potentiate digitalis arrhythmias in a manner that is inhibited by naloxone, and provide evidence that implicates a role for endogenous opioids in digitalis arrhythmias.Key words: digitalis arrhythmias, aminopeptidase inhibitors.