Kinetic disposition of (+)-S- and (-)-R-sotalol enantiomers in cardiac patients with tachyarrhythmias using an improved HPLC-fluorescence stereoselective method.
Since the enantioselective pharmacokinetic profiles of R,S-sotalol in cardiac patients are controversial, the present investigation aimed to study the kinetic disposition of sotalol enantiomers in patients with tachycardia. Thirteen cardiac patients, who gave their written consent, were included (6F/7M; 53 +/- 12 yrs, 66 +/- 13 kg, 163 +/- 8 cm height). They had tachycardia, normal renal function and had been chronically treated with tablets of sotalol 160 mg b.i.d. The patients were submitted to blood samples collection at zero, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after drug administration. The quantitation of sotalol enantiomers were performed by a stereoselective HPLC method with fluorescence detection previously published. A one open compartment model was applied and the main pharmacokinetic parameters obtained for R-/S-sotalol were, respectively (Mean +/- SD): CSSMAX = 1007 +/- 307/1040 +/- 340 ng/mL; TMAX = 1.82 +/- 0.6/1.83 +/- 0.6 h; AUCSST = 6959 +/- 2153/7388 +/- 2563 ng.h/mL; CISSr/F = 2.7 +/- 1.2/2.5 +/- 1.2 mL/min/kg and VdSS/F = 1.9 +/- 0.9/2.0 +/- 1.0 L/kg. The pharmacokinetic parameters of R,S-sotalol were within the published range and the kinetic parameters for the isomers were grouped as two independent samples and statistically compared. In conclusion, stereoselective pharmacokinetic for sotalol was not observed in cardiac arrhythmic patients, i.e., both R- and S-sotalol enantiomers have the same pharmacokinetic profile.
da Cunha
L C
LC
Faculdade de Farmácia-UFGO, Escola Paulista de Medicina-UNIFESP.
Gondim
F A A
FA
de Paola
A A V
AA
Barros
I C Medeiros
IC
Santos
S R Cavani Jorge
SR
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013015:Sotalol / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D000889:Anti-Arrhythmia Agents; D013015:Sotalol