Oral Lignocaine. Its Absorption and Effectiveness in Ventricular Arrhythmia Control

Abstract

A preliminary study suggests that the gastrointestinal absorption of lignocaine is predictable and that adequate antiarrhythmic blood concentrations are maintained for four to five hours when 500 mg. is taken with food and for two hours if the drug is taken without food. Ventricular arrhythmias were successfully treated with oral lignocaine in four patients.

Pharmacokinetics of lidocaine in man

“…These effects lasted approximately 15 to 20 minutes even though the lidocaine plasma levels remained elevated. The symptoms would appear to be similar to those reported by Eisinger and Hellier 5 and Parkinson and associates 12 during previous studies in which lidocaine was administered orally. It is interesting to note that such effects were not reported during either of the intravenous infusion experiments, although the lidocaine plasma levels were higher than those after the 500 mg. oral doses.…”

“…Our blood level data following oral administration of 250 and 500 mg. of lidocaine are not comparable with that reported by Parkinson and associates. 12 Even if all of the orally administered dose reached the systemie cireulation intact, it would seem improbable that blood levels as high as those reported would be attained. The most likely explanation for the discrepancy between our results and those presented by Parkinson and associates 12 is that the eolorimetrie assay procedure used by them was not specifie for unmetabolized lidocaine.…”

“…If this equality is maintained, the time at which the minimum blood level is attained, can be calculated by setting the derivative of Equation 2 to zero and solving for t. The resultant equation is Equation 12. (12) It should be noted that Equation 12 is independent of D 1 and b but requires that they be in a set ratio to each other as given by Equation 11. The actual blood level expected at this minimum can be calculated by substituting the value of t from Equation 12 into Equation 2, 01' more appropriately the ratio of this blood level to the steady-state level is determined by substituting t from Equation 12 into Equation 6.…”

“…5 , 12 Although these studies are limited in scope, there appears to be a considerable discrepancy in the reported blood levels. Parkinson and associates 12 reported levels of lidocaine ranging from approximately 5 to 16 fLg per milliliter for 250 and 500 mg. oral doses of lidocaine, whereas the highest plasma level found by Eisinger and Hellier 5 was 2.4 ftg per milliliter in one subject 30 minutes after 500 mg. of lidocaine orally. Because of the conflicting data, it is not pos-sible to predict at this time whether lidocaine would be a useful antiarrhythmic drug when administered orally.…”

Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients.

“…A value of approximately 70 min for the terminal half-life in normal subjects is considerably lower than commonly reported (Rowland et al, 1971;Rowland, 1974;Sasyniuk & Ogilvie, 1975), probably as a consequence of the relatively young age of the subjects studied (Nation, Triggs & Selig, 1977 & Rowland, 1975;Nation et al, 1977) appear to play an important role The kinetics of lignocaine after oral administration have been less extensively investigated. Although the drug has been administered orally in a number of studies Keenaghan & Boyes, 1972;Adjepon-Yamoah & Prescott, 1973;AdjeponYamoah, Scott & Prescott, 1974;Benowitz et al, 1974a;Finlayson, Prescott, Adjepon-Yamoah & Forrest, 1974;Bending et al, 1976) and therapeutic effectiveness of this route has been claimed (Parkinson & Margolin, 1970), available information on the plasma concentrations obtained after comparable doses is controversial (Eisinger & Hellier, 1969;Parkinson & Margolin, 1970;Boyes et al, 1971;Adjepon-Yamoah, Scott & Prescott, 1973). Our value of 37% for lignocaine bioavailability in normal subjects is in extremely good agreement with recent studies Bending et al, 1976) in which the serum concentration of the drug was measured by specific gas-chromatographic techniques.…”