The pharmacokinetics of toborinone in subjects with congestive heart failure and concomitant renal impairment and/or concomitant hepatic impairment.
The pharmacokinetics of toborinone was studied in subjects with congestive heart failure (CHF) and concomitant renal and/or hepatic disease. At the time of admission, subjects were grouped based on estimated creatinine clearance and serum bilirubin. Glomerular filtration rate was assessed using iothalamate clearance. Hepatic function was assessed using the caffeine metabolism test and indocyanine green clearance. No significant differences were observed in mean toborinone pharmacokinetic parameters among the four study groups. Positive correlations were observed between toborinone clearance and the measured indices of renal and hepatic function: creatinine clearance, iothalamate renal clearance, paraxanthine/caffeine ratio, and indocyanine green clearance. Toborinone clearance decreased with decreasing creatinine clearance, decreasing glomerular filtration rate, decreasing demethylation metabolic activity, and decreasing hepatic bloodflow, although no significant differences were observed in any mean toborinone pharmacokinetic parameters evaluated among the four study groups.
Tammara
Brinda
B
Otsuka America Pharmaceutical, Inc., Rockville, Maryland 20850, USA.
Trang
John M
JM
Kitani
Mami
M
Miyamoto
Gohachiro
G
Bramer
Steven L
SL
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D007677:Kidney Function Tests; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015203:Reproducibility of Results; D013997:Time Factors
D002316:Cardiotonic Agents; D007202:Indicators and Reagents; D015363:Quinolones; C077543:toborinone