Stereoselective pharmacokinetics of tocainide in human uraemic patients and in healthy subjects.
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.
McErlane
K M
KM
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Axelson
J
J
Vaughan
R
R
Kerr
C R
CR
Price
J D
JD
Igwemezie
L
L
Pillai
G
G
D000328:Adult; D005260:Female; D006207:Half-Life; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D013237:Stereoisomerism; D016677:Tocainide; D014511:Uremia / Q000097:blood / Q000378:metabolism*
D016677:Tocainide; D008012:Lidocaine