title: The role of digitalis pharmacokinetics in converting atrial fibrillation and flutter to regular sinus rhythm.
abstract: This report examined the role of digitalis pharmacokinetics in helping to guide therapy with digitalis glycosides with regard to converting atrial fibrillation (AF) or flutter to regular sinus rhythm (RSR). Pharmacokinetic models of digitoxin and digoxin, containing a peripheral non-serum effect compartment, were used to analyze outcomes in a non-systematic literature review of five clinical studies, using the computed concentrations of digitoxin and digoxin in the effect compartment of these models in an analysis of their outcomes. Four cases treated by the author were similarly examined. Three literature studies showed results no different from placebo. Dosage regimens achieved ≤11 ng/g in the model's peripheral compartment. However, two other studies achieved significant conversion to RSR. Their peripheral concentrations were 9-14 ng/g. In the four patients treated by the author, three converted using classical clinical titration with incremental doses, plus therapeutic drug monitoring and pharmacokinetic guidance from the models for maintenance dosage. They converted at peripheral concentrations of 9-18 ng/g, similar to the two studies above. No toxicity was seen. Successful maintenance was achieved, using the models and their pharmacokinetic guidance, by giving somewhat larger than average recommended dosage regimens in order to maintain peripheral concentrations present at conversion. The fourth patient did not convert, but only reached peripheral concentrations of 6-7 ng/g, similar to the studies in which conversion was no better than placebo. Pharmacokinetic analysis and guidance play a highly significant role in converting AF to RSR. To the author's knowledge, this has not been specifically described before. In my experience, conversion of AF or flutter to RSR does not occur until peripheral concentrations of 9-18 ng/g are reached. Results in the four cases correlated well with the literature findings. More work is needed to further evaluate these provocative findings.
authors.affiliation: Laboratory of Applied Pharmacokinetics, Keck School of Medicine, University of Southern California, Children's Hospital of Los Angeles, MS # 51, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA, jelliffe@usc.edu.
authors.forename: Roger W
authors.initials: RW
authors.lastname: Jelliffe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001282:Atrial Flutter / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004070:Digitalis; D004074:Digitoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D004074:Digitoxin