Biomedical subjects

D M DiPersio

Publications and source records attributed to D M DiPersio.

5 recordsLinked to original sources

PubMed1991

The effect of CPR on plasma diltiazem concentrations in dogs.

STUDY OBJECTIVE: To determine the effect of cardiac arrest with CPR on diltiazem concentrations in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large university-affiliated medical center. TYPE OF PARTICIPANTS: Twenty mongrel dogs. INTERVENTIONS: Following administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, and right ventricle. Dogs were randomized to receive diltiazem (0.5 mg/kg) either 60 minutes before or during cardiac arrest with CPR. After 13 minutes of cardiac arrest, defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: Frequent blood samples for diltiazem concentrations were obtained before, during, and after cardiac arrest. The mean diltiazem concentration rose 70% during CPR in the group that received diltiazem before cardiac arrest. The group that received diltiazem during CPR had concentrations five times greater than expected during sinus rhythm. CONCLUSION: Increased diltiazem concentrations are observed during CPR and are probably related to altered distribution encountered during CPR.

Animals↗

PubMed1988

Clinical pharmacokinetics of controlled-release disopyramide in patients with cardiac arrhythmias.

UNLABELLED: The pharmacokinetics of the controlled-release preparation of disopyramide phosphate (Norpace CR, Searle Laboratories, Chicago, IL) were studied in ten patients with cardiac arrhythmias. Multiple-serum disopyramide concentrations were obtained after a 300-mg oral dose. Each patient then received chronic oral therapy with the controlled-release preparation (400 to 1000 mg/day) on an every-12-hour schedule. At steady state, disopyramide trough concentrations were obtained. Serum disopyramide concentrations were determined by high performance liquid chromatography. The regimen was well tolerated by all patients. The mean (+/- SD) time to maximum concentration, maximum concentration, and concentrations 11 and 24 hours after the initial dose were 5.5 +/- 1.3 hours and 2.8 +/- 0.8, 2.0 +/- 0.9, and 1.2 +/- 0.5 micrograms/mL, respectively. A low Cmax to trough concentration ratio of 1.35 +/- 0.26 was observed after the initial dose. Linear regression analysis of the serum disopyramide concentrations 11 hours after initial dose (trough) versus trough concentrations at steady state (dose adjusted) showed a strong correlation (r = 0.87, intercept = 0.03, and slope = 1.9). Regression analysis also showed a strong relationship between the area under the curve (AUC) from time 0 to 11 hours after the initial dose and the trough at steady state (r = 0.86). CONCLUSIONS: The controlled-release preparation of disopyramide, when administered every 12 hours in patients with cardiac arrhythmias, should produce low peaks to trough fluctuations. Because disopyramide concentrations after the initial dose correlate well with trough concentrations at steady state, these concentrations may provide a simple and convenient method for prospective monitoring of disopyramide therapy in patients receiving the controlled-release preparation.

Adult↗

PubMed1987

Transfer from immediate-release disopyramide to controlled-release disopyramide.

Simulation of serum disopyramide concentrations during transfer from steady-state immediate-release (IR) disopyramide to a sustained-release disopyramide preparation was performed based on pharmacokinetic parameters obtained from IR disopyramide and serum concentrations measured following an initial dose of controlled-release (CR) disopyramide phosphate. Based on the results of simulation, a typical patient with good cardiac, renal, and hepatic function can be transferred from a q 6 h IR disopyramide to an equivalent daily dose of controlled-release disopyramide administered q 12 h beginning at 6 hours after the final IR disopyramide dose.

Anti-Arrhythmia Agents↗

PubMed1985

Antifibrillatory effects of lidocaine and bretylium immediately postcardiopulmonary resuscitation.

The antifibrillatory effects of lidocaine and bretylium in the postcardiopulmonary resuscitation (CPR) setting were examined using ventricular fibrillation threshold (VFT) determinations in anesthetized dogs. The dogs were fibrillated and CPR was carried out with a pneumatic device. Lidocaine and bretylium were administered intravenously at the onset of CPR, and VFT was serially determined after defibrillation following three consecutive 3-minute CPR periods. A dose of 2 mg/kg of lidocaine caused a significant increase in VFT determinations after the first but not subsequent 3-minute CPR periods; a dose of 1 mg/kg of lidocaine was ineffective at any time point. A dose of 5 mg/kg of bretylium elevated the VFT after the second and third but not the first 3-minute period. In dogs who received lidocaine, a significant elevation of VFT determinations were found to be associated with a high blood lidocaine concentration (mean 13.8 +/- 8.3 micrograms/ml). The present study demonstrates that a 2 mg/kg dose of lidocaine administered during CPR rapidly increases VFT determinations after CPR (within 5 minutes), whereas, a 5 mg/kg dose of bretylium significantly elevates VFT determinations but at a later time (within 10 minutes). The observed significant effect of lidocaine appears to be associated with high lidocaine blood concentrations (greater than 6 micrograms/ml).

Animals↗

PubMedDate not supplied

Predicting plasma procainamide concentrations resulting from a sustained-release preparation.

Two methods of predicting plasma procainamide concentrations (PPCs) for a sustained-release procainamide (SRP) dosage form were compared using previously published data on 12 healthy subjects. Methods A and B were both based on a one-compartment pharmacokinetic model requiring an elimination rate constant and area under the concentration-time curve from an immediate-release oral procainamide dosage form and in vitro dissolution data from the SRP product. Method A also used an absorption rate constant. The predicted versus measured PPCs for two sets of peak and trough concentrations in each subject were evaluated using linear regression. The mean predicted PPCs by both methods followed the measured PPCs closely; however, the time of peak concentration was predicted more accurately by method A. The evaluation of predictive performance showed good precision and a small but statistically significant bias with either method, peak values were overpredicted and trough values were underpredicted. These two methods adequately predicted plasma procainamide concentrations in healthy subjects following a sustained-release procainamide preparation.

Delayed-Action Preparations↗