digoxin and Obesity--Morbid

Fourteen obese patients (body mass index = 34-47 kg/m2; mean = 40 kg/m2) with lumbar cerebrospinal fluid pressure (Pcsf) above 20 cm water in 10 of the 14 patients were treated with digoxin with a serum concentration of at least 1.0 nmol/L (0.8 ng/ml) for 6 months. Pcsf decreased significantly during digoxin medication (p < 0.005). Although there were no diet restrictions, all patients decreased in weight (range: 3-25 kg; mean = 10.6 kg) during the 6 months (p < 0.001). When digoxin medication was stopped in 3 patients, prompt weight increase occurred. Most patients needed progressively increased digoxin doses to attain stabilized serum concentrations at the stipulated level, in 5 patients more than 0.5 mg a day. Five of 13 patients developed diabetes mellitus during the digoxin medication. The larger the dose of digoxin, the greater the risk for diabetes mellitus to occur.

Topics: Adult; Body Mass Index; Body Weight; Cerebrospinal Fluid Pressure; Diabetes Mellitus; Digoxin; Female; Humans; Intracranial Hypertension; Middle Aged; Obesity, Morbid; Time Factors; Treatment Outcome; Weight Loss

Roux-en-Y gastric bypass surgery (RYGBS) is an effective surgical intervention to reduce mortality in morbidly obese patients. Following RYGBS, the disposition of drugs may be affected by anatomical alterations and changes in intestinal and hepatic drug metabolizing enzyme activity. The aim of this study was to better understand the drug-drug interaction (DDI) potential of CYP3A and P-gp inhibitors. The impacts of RYGBS on the absorption and metabolism of midazolam, acetaminophen, digoxin, and their major metabolites were simulated using physiologically-based pharmacokinetic (PBPK) modeling. PBPK models for verapamil and posaconazole were built to evaluate CYP3A- and P-gp-mediated DDIs pre- and post-RYGBS. The simulations suggest that for highly soluble drugs, such as verapamil, the predicted bioavailability was comparable pre- and post-RYGBS. For verapamil inhibition, RYGBS did not affect the fold-change of the predicted inhibited-to-control plasma AUC ratio or predicted inhibited-to-control peak plasma concentration ratio for either midazolam or digoxin. In contrast, the predicted bioavailability of posaconazole, a poorly soluble drug, decreased from 12% pre-RYGBS to 5% post-RYGBS. Compared to control, the predicted posaconazole-inhibited midazolam plasma AUC increased by 2.0-fold pre-RYGBS, but only increased by 1.6-fold post-RYGBS. A similar trend was predicted for pre- and post-RYGBS inhibited-to-control midazolam peak plasma concentration ratios (2.0- and 1.6-fold, respectively) following posaconazole inhibition. Absorption of highly soluble drugs was more rapid post-RYGBS, resulting in higher predicted midazolam peak plasma concentrations, which was further increased following inhibition by verapamil or posaconazole. To reduce the risk of a drug-drug interaction in patients post-RYGBS, the dose or frequency of object drugs may need to be decreased when administered with highly soluble inhibitor drugs, especially if toxicities are associated with plasma peak concentrations.

Topics: Acetaminophen; Administration, Oral; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B; Biological Availability; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Digoxin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Gastric Bypass; Gastrointestinal Absorption; Hepatobiliary Elimination; Humans; Intestinal Elimination; Metabolic Clearance Rate; Midazolam; Models, Biological; Obesity, Morbid; Postoperative Period; Triazoles; Verapamil

Topics: Amiodarone; Anti-Arrhythmia Agents; Appendicitis; Belgium; Digoxin; Drug Information Services; Humans; Iatrogenic Disease; Male; Medication Errors; Medication Reconciliation; Middle Aged; Obesity, Morbid; Pharmacists; Postoperative Complications

An ethylic hypertensive patient with a BMI of 51.4 developed persistent atrial fibrillation with high ventricular rates. External electrical cardioversion was attempted, but failed in spite of high energy shocks (350 joules). Sinus rhythm was restored by internal cardioversion (12 joules). The value and indications of the techniques are briefly discussed.

Topics: Alcoholism; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Body Mass Index; Chronic Disease; Combined Modality Therapy; Digoxin; Electric Countershock; Humans; Hypertension; Male; Middle Aged; Obesity, Morbid; Patient Selection