topeeng.gif (8383 bytes)

[ Scientific Activity - Actividad Científica ] [ Brief Communications - Temas Libres ]

Effects of the slow-releasing oral Lidocaine in suppression of ventricular arrhytmia in patients after myocardial infarction.

Ioan Axente Gutiu*, Victor Voicu**, Constantin Mircioiu**, Mariana Jinga**, Laurentiu Ioan Gutiu**

*- St. Mary Hospital
**- Army Research Center
Bucuresti, Romania

Abstract
Aim
Background
Method
Results
Discussion
Conclusions
References

Abstract
Background: Lidocaine is an efficient anti-arrhythmic drug used intensively on intravenous way. But our pharmacodynamic/pharmacokinetic studies on the supposed effects of oral slow-releasing Lidocaine proved that this drug can be used as a useful drug in treatment of ventricular arrhythmia, by mouth, in many clinical situations. In this preliminary study we analyse the effects of oral Lidocaine on ventricular arrhythmia in patients after myocardial infarction.
Subjects: We studied 14 patients with myocardial infarction in their recent history (the past 6 months). Mean age 62 years; 11 males, 3 women.
Method: Initially, after a 24 hours Holter monitoring, we gave to patient slow-releasing Lidocaine in tablets of 350 mg, three-times in day. In following day, we repeated the Holter monitoring and then, the tape analysis.
Results: The results in the table show the significant reduction of the ventricular premature beats, of salvos and of ventricular tachycardia episodes.

tab1.gif (2148 bytes)

 

We did not noted important side effects of this treatment, only moderate dizziness in 2 patients, at 25-30 minutes after the second dose. Conclusion: This preliminary study show that oral slow-releasing Lidocaine is efficient in treatment of the ventricular arrhythmia in the patients in recent stage after myocardial infarction. However, is necessary a more large clinical study with the serum determination of the drug for establishing of the all therapeutic capacity.

Top

Aim:  We have undertaken this study in order to demonstrate that some pharmaceutical conditioning, not specific for a certain drug, could be effective, more flexible, with less adverse events.

Background:  It is well known that lidocain is used as an antiarrhytmic drug and administered mainly in perfusion but for a long time it have been tried different variants of oral lidocaine.

A group of scientists from the Army Research Center developed an oral pharmaceutical conditioning of lidocaine, with slow releasing by including the active substance in a matrix of low pressure polyethilene, obtaining a tablet of 325 mg of slow releasing lidocaine.

The pharmacokinetics beeing encouraging, blood dosing of the lidocain (gas-cromatography) showing that therapeutic concentrations have been reached, lidocain blood levels being relatevily steady after the administration of 1 tablet each 8 hours, we decided that in this conditions a therapeutic pre-test was necessary.

Top

Method: We have studied a group of 14 patients with ventricular arrhytmia occurred after a miocardial infarction.

We performed 2 ECG-Holter recordings of 24 hours each, one before and the other after the treatment with lidocaine oraly (3 tablets per day).

We have analized the number of ventricular ectopic beats before and after the treatment, heart rate variability indices.

Results: The number of total ventricular ectopic beats decreased in 13 patients a decreasing being observed also in the frequence of the ventricular ectopic runs and episodes of ventricular tahicardia a more clear view being available in table 1, table 2, table 3 and figure 1.

Table 1: Characteristics of the studied group
tabla1.gif (11005 bytes)

Table2: Principal results
tabla2.gif (12494 bytes)
References: LVF: left ventricular failure; PMIA post MI angina; AH: arterial hypertension; EA: exertion angina;
IHD: ischemic heart disease; HF: heart failure; S: sequel; T: total; VEB: ventricular ectopic beats; VT: ventricular
tachycardia; MF: mean frequency; PreL: pre lidocaine; PostL: post lidocaine; C: corrected.

Table 3: Effects of lidocaine on heart rate variability
tabla3.gif (12474 bytes)
refer.gif (5497 bytes)

graf1.gif (28990 bytes)
Fig. 1

Top

Discussion: The results were encouraging but the number of patients is low and in this case the statistics are not so accurate. We think that is necessary and we prepare a more complex study, randomized and double-blind with a concomitant pharmacokinetic profile and the possibility of the dose adjustement, in this case a final conclusion will be possible.

Conclusions: The oral pharmaceutical conditioning of the lidocain seems to be effective in the treatment of arrhytmias, therapeutic blood levels being reached in 24 hours after 3 tb/day.

The effects on the variability of the heart rate is not statisticaly significant.

We didn’t observe any adverse event, and the digestive tolerability was very good.

Top

References

  1. ARVELA P., RAUTIO A., SATANIEMI G. A. - "Lidocain metabolism as a liver function test" in Cytocrome P450 - Paris, 1994, 777-779
  2. BAILEY J. M. - "Pharmacometrics - A Technique for Calculating the Mean Time for Equilibration of Drug Distribution Using Minimal Structural Assumptions" - J. Pharmacokin. Biopharmaceut., 1994, 22: 157-164
  3. BJORNSSEN T. D., LUI N. L., ENGLAND M. J. - "Estimation of Pharmacokinetic Parameters for Simulations of Time Courses of drug concentrations after Oral Administration" - J. Clin. Pharmacol., November, 1994, 34: 1046-1052
  4. BRAUNWALD E. - "Heart Disease - A Textbook of Cardiovascular Medicine" - Fourth Edition, 1993
  5. COLATSKY T. J. - "The Sicilian Gambit and antiarrhythmic drug development" - Cardiovasc. Res., 1992, 26: 562-565
  6. DOBRESCU D. - "Farmacoterapie practica" - vol. 1 si 2, Editura Medicala, Bucuresti, 1989
  7. FEHMERS M., DUNNING A. - "Intramuscularly and orally administred lidocaine in the treatment of ventricular arrhytmias in acute myocardial infarction" - Am. J. Cardiol., 1972, 29: 514
  8. GITLAN I., MIRCIOIU C., SANDU E. - "Cercetari privind realizarea unor comprimate antiaritmice pe baza de xilina II. Cinetica de cedare in vitro." - Rev. San. Mil.,1987, 90: 87
  9. GOODMAN A., RALL T.W., NIES A. S., TAYLOR P. - "Goodman and Gilman’s - The Pharmacological Basis of Therapeutics" - in two volumes - 1991
  10. VOICU V., MIRCIOIU C., JINGA M., IONESCU M., BURCEA X., IONESCU D.D., LUPESCU G. - "Pharmacokinetic based adjustment of lidocaine antiarrhythmic shedule" - Europ. J. Drug Metabol. Pharmacokin., 1994, vol 19: 33-36

Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to pharma-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.

Top


© CETIFAC
Bioengineering
UNER

Update
Dic/23/1999


This company contributed to the Congress:

 

bayer.gif (2605 bytes)

adalip.gif (17403 bytes)

lip_ada.gif (19392 bytes)