Stereoselective pharmacokinetics of tocainide in human uraemic patients and in healthy subjects

✍ Scribed by K. M. McErlane; J. Axelson; R. Vaughan; C. R. Kerr; J. D. Price; L. Igwemezie; G. Pillai

• Publisher: Springer
• Year: 1990
• Tongue: English
• Weight: 440 KB
• Volume: 39
• Category: Article
• ISSN: 0031-6970
• DOI: 10.1007/bf00315413

✦ Synopsis

The disposition of tocainide enantiomers were examined in healthy human subjects and uraemic patients following a single i.v. dose (200 mg) of racemic tocainide hydrochloride. In the healthy subjects, the total body clearance of R(-)-tocainide was significantly greater than that of S(+)-tocainide (2.62 vs 1.70 ml.min-1.kg-1). Renal clearance also favoured R(-)-tocainide and appeared to contribute significantly to the stereoselective total body clearance. The volume of distribution of the enantiomers did not differ significantly. Uraemia produced a marked decrease in the total body clearance with no apparent effect on the volume of distribution of both enantiomers. The S/R ratio for total body clearance decreased significantly from 0.66 in healthy subjects to 0.54 in the uraemics, while the ratio for terminal elimination half-life significantly increased from 1.43 to 1.59. These results indicate that uraemia alters the degree of stereoselectivity in the pharmacokinetic parameters of tocainide enantiomers.