THE INFLUENCE OF URINARY pH ON THE ELIMINATION OF MEXILETINE

Kiddie, Moira A.; Kaye, C M; Turner, Paul; Shaw, T. R. D.

doi:10.1111/j.1365-2125.1974.tb00241.x

Cited by 44 publications

(8 citation statements)

References 12 publications

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“…The results of this study confirm the observations of Kiddie, Kaye & Turner (1974) that both urinary excretion and plasma concentration of mexiletine are affected by urinary pH. The investigators in that study modified their volunteer's urinary pH to produce the effect, but we have been able to demonstrate it during spontaneous fluctuations in urinary pH.…”

Section: Discussionsupporting

confidence: 88%

The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers.

Johnston¹,

Burgess²,

Sj³

et al. 1979

Brit J Clinical Pharma

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1 The effect of spontaneous changes in urinary pH on renal excretion and plasma concentration of mexiletine has been examined during chronic administration of subtherapeutic doses of the drug to healthy volunteers. 2 Significant correlations were found between urinary pH and the plasma concentration and renal excretion of mexiletine. 3 Prediction of plasma mexiletine concentrations from our data suggests that the amount of mexiletine in plasma would increase by more than 50% following a rise in urinary pH similar to that' which occurred spontaneously in our subjects. 4 Factors which influence urinary pH should be considered when the dosage of mexiletine is chosen. Extremes of urinary pH may account for some cases of inefficacy of the drug, and for the occurrence of unwanted effects at conventional doses. IntroductionMethods

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Section: Discussionsupporting

confidence: 88%

The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers.

Johnston¹,

Burgess²,

Sj³

et al. 1979

Brit J Clinical Pharma

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“…Between individual patients there were great variations in the kinetics with all modes of administration and this was reflected in the great variation in plasma concentrations. Kiddie, Kaye, Turner & Shaw (1974) suggested that this variation might partly be due to fluctuations in urinary pH. They showed that altering the pH of the urine markedly affected the elimination half-life of mexiletine by altering the urinary excretion of unchanged drug.…”

Section: Discussionmentioning

confidence: 99%

The clinical pharmacology of mexiletine.

Campbell¹,

Kelly²,

Adgey³

et al. 1978

Brit J Clinical Pharma

129

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1Mexiletine was given to 156 patients by intravenous or oral routes of administration. 2 There was great interpatient variation in kinetics and plasma concentrations with both routes of administration. 3 The mean volume of distribution was 6.63 1/kg. The mean plasma elimination half-life after chronic oral therapy was 11.31 h.4 Plasma concentrations between 0.75 and 2.00 gg/ml were usually effective. Within this therapeutic range severe side effects were uncommon. 5Plasma concentrations within this range were achieved in 72% of patients when doses of 10-14 mg-' kg-l day were given orally.

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“…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).…”

Section: Discussionmentioning

confidence: 95%

Mexiletine in Treatment of Ventricular Arrhythmias

Stavenow

Hanson

Johansson

1979

Journal of Internal Medicine

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ABSTRACT. Mexiletine, a new drug effective in the treatment of ventricular arrhythmias, was given to 20 patients for approximately 2 years. The study was designed to investigate the nature and prevalence of side‐effects during long‐term therapy, and the degree of correlation between such effects and the serum level of the drug. The methodology used to determine the serum level is described. Mexiletine was well tolerated and serious side‐effects were not seen. In particular, antinuclear factor was not detected during the treatment period. The serum level of mexiletine was easily maintained within the therapeutic range, and most side‐effects correlated closely with the drug level. Mexiletine appears to be an effective alternative to currently available antiarrhythmic agents.

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THE INFLUENCE OF URINARY pH ON THE ELIMINATION OF MEXILETINE

Cited by 44 publications

References 12 publications

The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers.

The effect of spontaneous changes in urinary pH on mexiletine plasma concentrations and excretion during chronic administration to healthy volunteers.

The clinical pharmacology of mexiletine.

Mexiletine in Treatment of Ventricular Arrhythmias

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