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Chew, C.; Collett, J.; Singh, B.
doi: 10.2165/00003495-197917030-00003pmid: 378646
Synopsis: Mexiletine2 is a new local anaesthetic antiarrhythmic agent whose chemical structure and electrophysiological properties closely resemble those of lignocaine although its anticonvulsant and pharmacokinetic properties differ from that drug. Unlike lignocaine (lidocaine) it is active following oral administration with a plasma half-life varying between 8 and 20 hours so that it can be administered twice or three times daily to sustain therapeutic plasma levels. The drug is effective when given intravenously or by the oral route in controlling ventricular arrhythmias especially following acute myocardial infarction but the side effects are greater during parenteral administration. Side effects during chronic oral therapy with mexiletine have not posed a serious problem. Mexiletine has the pharmacodynamic and pharmacokinetic properties of an agent suitable for the chronic oral prophylaxis of serious ventricular arrhythmias in patients with ischaemic heart disease.
Roberts, R.; Desmond, P.; Schenker, Steven
doi: 10.2165/00003495-197917030-00005pmid: 378647
Liver disease in man is associated with a variety of pathophysiological processes which may influence the disposition of drugs in several ways. Interpretation of the observed pharmacokinetic changes in liver disease requires an understanding of the relationship between systemic drug clearance (Cls), volume of distribution (Vd)and the elimination half-life [t1/2(β)], i.e. t1/2(β) = 0.693· Vd/Cls.Half-life will be a measure of the fluctuation in drug level one may expect with continued administration of a drug while clearance will determine the dose required to achieve a particular steady state level. Liver disease may affect clearance and volume of distribution and so produce changes in half-life; in addition, alterations in plasma binding of drugs may occur and so influence free (unbound) drug levels. It is also possible that the end organ response, particularly in the case of sedative drugs, may be affected by liver disease.
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