Abstract:
:The pharmacokinetics of mexiletine and its metabolite hydroxy-methyl-mexiletine have been investigated following single-dose and during multiple-dose administration of a sustained-release form of mexiletine to six post-myocardial infarct patients. Comparison of single-dose and washout pharmacokinetics, after short-term multiple-dose administration, showed significant (p < 0.005), but not systematic, modifications in mexiletine apparent clearance for three patients. Furthermore, for these patients, simulation with both sets of parameters indicated that the steady-state was achieved before washout experiment in two cases. The fraction of mexiletine metabolized to hydroxy-methyl-mexiletine was lower for multiple-dose administration (about 18 per cent) than for the single dose (about 42 per cent). The hydroxy-methyl-mexiletine elimination rate constant was about four times that of mexiletine. Mexiletine clearance could be accounted for by other metabolic pathways. In one patient, hydroxy-methyl-mexiletine was undetectable even during multiple-dose administration, despite a significant increase in mexiletine clearance. However, the observed changes in mexiletine disposition had no therapeutic implications and active plasma levels were achieved by the third day of administration and maintained in the therapeutic range (0.75 to 2 micrograms ml-1) in all patients after a twice daily dosage regimen.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Bruno R,Santoni Y,Iliadis A,Djiane P,Serradimigni A,Cano JPdoi
10.1002/bdd.2510130702keywords:
subject
Has Abstractpub_date
1992-10-01 00:00:00pages
481-93issue
7eissn
0142-2782issn
1099-081Xjournal_volume
13pub_type
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