THE RENAL EXCRETION OF MEXILETINE (Kö 1173) UNDER CONTROLLED CONDITIONS OF URINE pH

Mexiletine in Treatment of Ventricular Arrhythmias

“…In view of the metabolic processes involved, it is possible that the rate of metabolism may be influenced by smoking or exposure to enzyme-inducing agents such as phenobarbitone, The percentage of unchanged drug in the urine is pH-dependent. At normal urinary pH, amounts of 10-23 %of ingested doses are recovered unchanged, but this value rises to almost 50% at pH 5.0 and falls to almost negligible amounts at pH 8.0 (9,10).…”

Is there an ideal antiarrhythmic drug? A review — with particular reference to class I antiarrhythmic agents

“…Elliot et al (1959) found that urinary pH varies widely in a normal population and it follows a circadian rhythm. Urinary excretion of some antiarrhythmic drugs such as lignocaine and mexiletine is pHdependent; the amount excreted is higher when the urine is acidic than when it is alkaline (Kiddie & Kaye, 1974, 1976. This also applies to flecainide, the urinary excretion of which under acidic conditions is greater than under alkaline conditions (Muhiddin et al, 1984).…”

Enhanced metabolism of mexiletine after phenytoin administration.

“…As the renal clearance of unchanged mexiletine is very sensitive to change in the urinary pH (Prescott et al, 1977;Johnston et al, 1979;Kiddie & Kaye, 1974;Beckett & Chidomere, 1977) the pH was controlled in subjects 2 to 6 by administering one capsule (10 mEq) of sodium bicarbonate five times per day from 48 h prior to each mexiletine administration to the end of blood sampling. Urine pH was monitored throughout the blood sampling period and remained between 7 and 8 pH units.…”