Pharmacokinetics of mexiletine in renal insufficiency.

Allaf, Dia El; Henrard, L; Crochelet, Luc; Delapierre, D.; Carlier, J; Dresse, A

doi:10.1111/j.1365-2125.1982.tb02003.x

Cited by 34 publications

(12 citation statements)

References 10 publications

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“…The results indicate that peritoneal dialysis removes very little mexiletine. The total body clearance was similar to that reported previously in renal failure patients (Jones et al, 1983;El Allaf et al, 1982). It must be recognized that this is an apparent total body clearance since the fraction absorbed had to be estimated (88%).…”

Section: Mexiletine Clearance During Peritoneal Dialysissupporting

confidence: 84%

“…The effect of haemodialysis on mexiletine pharmacokinetics is unknown. Renal impairment itself has little effect on the pharmacokinetics of mexiletine until the creatinine clearance is reduced to less than 10 ml/min, at which point the total body clearance is slightly reduced from the 6-13 ml min-1 kg1 noted in normal volunteers and patients with normal renal function (Haselbarth et al, 1981;Campbell et al, 1978) to 2.4-9.9 ml min-' kg-1 (El Allaf et al, 1982). A patient requiring mexiletine therapy while admitted to the intensive care unit provided the opportunity to assess the peritoneal clearance of mexiletine.…”

Section: Mexiletine Clearance During Peritoneal Dialysismentioning

confidence: 99%

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Mexiletine clearance during peritoneal dialysis [letter]

Guay¹,

Meatherall²,

Ferguson³

et al. 1985

Brit J Clinical Pharma

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Section: Mexiletine Clearance During Peritoneal Dialysissupporting

confidence: 84%

Section: Mexiletine Clearance During Peritoneal Dialysismentioning

confidence: 99%

Mexiletine clearance during peritoneal dialysis [letter]

Guay¹,

Meatherall²,

Ferguson³

et al. 1985

Brit J Clinical Pharma

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“…Hence in most subjects normal physiological changes in urine pH seem unlikely to have a clinically significant effect on meiletine steadystate plasma concentrations or half-life (Prescott et al, 1977;El Allaf et al, 1982). However, we found, as did Johnston et al (1979) that in some individuals the changes are greater and could affect the outcome of therapy.…”

Section: Discussionmentioning

confidence: 48%

“…Changes in half-life, when they occurred, were not always due to changes in total plasma clearance because of the unpredictable effects of acidification on distribution volume. The renal contribution to elimination of mexiletine is minor and the plasma kinetics are not influenced by mild to moderate renal failure (El Allaf et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Mexiletine disposition: individual variation in response to urine acidification and alkalinisation.

Mitchell¹,

Clements²,

Pottage³

et al. 1983

Brit J Clinical Pharma

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Edinburgh Royal Infirmary, Edinburgh 1 The disposition of mexiletine has been studied in five subjects on two occasions with urine pH controlled at 5.0 and at 8.0. 2 With acid urine total plasma clearance was similar in all subjects (462 to 497 ml min-') and the plasma half-life ranged from 3.8 to 9.2 h (mean 6.7 h). With alkaline urine the total plasma clearance varied considerably (239 to 441 ml min-'); the mean half-life, 9.7 h, (range 7.6 to 12.7 h) was not significantly different from that in the acid urine study. 3 Renal clearance fell greatly in every subject on alkalinisation of the urine. The total plasma clearance fell by a similar amount in two. In the remaining three the fall in total clearance was much smaller because of an increase in non-renal clearance. The reduction in total plasma clearance only just achieved statistical significance. 4 The increase in predicted steady-state plasma mexiletine concentrations during infusion with change in urine pH from 5 to 8 varied between +5% and +95% (mean +39%).5 Changes in urine pH have a predictable effect upon renal clearance of mexiletine. However, disposition is changed in an unpredictable manner and inter-subject variation in distribution volume and non-renal clearance are important factors.

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“…Variations in intersubject distribution volumes and non-renal clearance appear to be important factors. EI Allaf et al (1982) administered mexiletine to patients with chronic renal failure. The elimination half-life was significantly elevated in the subgroup with a creatinine clearance of less than 10 mljmin compared with controls (15.7 vs lOAh), whereas the elimination half-life (13.8h) for those patients with a creatinine clearance between 10 and 30 mlj min did not differ significantly from controls.…”

Section: Variations In Urinary Phmentioning

confidence: 99%

Clinical Pharmacokinetics of the Newer Antiarrhythmic Agents

Gillis

Kates

1984

Clinical Pharmacokinetics

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This article reviews clinical pharmacokinetic data on 8 new antiarrhythmic agents. Some of these drugs have been studied extensively while others are relatively new, with incomplete data due to limited evaluation. Amiodarone is a class III antiarrhythmic drug which is effective in treating many atrial and ventricular arrhythmias that are refractory to other drugs. Amiodarone accumulates extensively in tissues and its disposition characteristics are best described by models with 3 and 4 compartments. Its apparent volume of distribution is very large (1300 to 11,000L) and its elimination half-life very long (53 days). A delay of up to 28 days from of treatment to onset of antiarrhythmic effect may be observed, and the antiarrhythmic effect may persist for weeks to months following cessation of therapy. Clinically significant drug interactions have been observed with amiodarone and warfarin, digoxin, quinidine and procainamide. Encainide is a class Ic antiarrhythmic drug. Although it has a short elimination half-life (1 to 3h), 2 major metabolites with antiarrhythmic effects accumulate in the plasma of patients during long term therapy. Plasma concentrations of O-demethyl encainide appear to correlate with the antiarrhythmic effect. Flecainide, another class Ic antiarrhythmic agent, has an elimination half-life of 14 hours which makes it suitable for twice daily dosing. Flecainide elimination is prolonged in patients with low output heart failure. Significant drug interactions with digoxin and cimetidine have been reported. Lorcainide is also a class Ic antiarrhythmic drug, the bioavailability of which is nonlinear. Clearance of the drug is reduced during long term therapy. A major active metabolite, norlorcainide, accumulates in the plasma of patients during long term therapy and its concentration exceeds that of lorcainide by a factor of 2. The elimination half-lives of lorcainide (9h) and norlorcainide (28h) allow for once or twice daily dosing. Mexiletine, a class Ib antiarrhythmic drug, is structurally similar to lignocaine (lidocaine). A sustained release formulation provides effective plasma concentrations when administered twice daily. The apparent volume of distribution of mexiletine is 5.0 to 6.6 L/kg, and the elimination half-life varies from 6 to 12 hours in normal subjects and from 11 to 17 hours in cardiac patients. Mexilitine is extensively metabolised but the metabolites are not pharmacologically active. Renal elimination of mexiletine is pH dependent. Drugs which induce hepatic metabolism significantly alter the pharmacokinetics of mexiletine.(ABSTRACT TRUNCATED AT 400 WORDS)

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Pharmacokinetics of mexiletine in renal insufficiency.

Cited by 34 publications

References 10 publications

Mexiletine clearance during peritoneal dialysis [letter]

Mexiletine clearance during peritoneal dialysis [letter]

Mexiletine disposition: individual variation in response to urine acidification and alkalinisation.

Clinical Pharmacokinetics of the Newer Antiarrhythmic Agents

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