Pharmacokinetics of nicotine in kidney failure.
BACKGROUND
Smoking is an important risk factor for cardiovascular and cerebrovascular complications in patients with chronic kidney failure. Very high plasma nicotine concentrations have been reported in patients with severe kidney failure, indicating that the disposition of nicotine in these patients may be different. The purpose of this study was to assess the pharmacokinetics of intravenously administered nicotine in healthy subjects and in patients with kidney failure.


METHODS
Nine healthy subjects (glomerular filtration rate [GFR], 84 to 143 mL/min/1.73 m2), four patients with mild kidney failure (GFR, 63 to 73 mL/min/1.73 m2), five patients with moderate kidney failure (GFR, 18 to 36 mL/min/1.73 m2), and six patients with severe kidney failure (GFR, 1 to 10 mL/min/1.73 m2) were recruited. Three patients were treated with continuous ambulatory peritoneal dialysis. An intravenous infusion of nicotine (0.028 mg/kg) was given for 10 minutes. Nicotine and cotinine concentrations were measured in plasma, urine, and peritoneal dialysate from 0 to 24 hours after start of infusion


RESULTS
There were significant correlations between GFR and total clearance, nonrenal and renal clearance of nicotine, area under the plasma concentration-time curve extrapolated to infinity, terminal elimination half-life, and mean residence time. Nonrenal clearance was 1303 mL/min and 661 mL/min in healthy subjects and patients with severe kidney failure, respectively. Only 1% to 2% of the nicotine dose was excreted unchanged in a 24-hour collection of peritoneal dialysate. The elimination of cotinine was also decreased in patients with kidney failure.


CONCLUSIONS
Progressive kidney failure is associated with a gradual decrease of renal and nonrenal elimination of nicotine.
Molander
L
L
Department of Clinical Pharmacology, Pharmacia & Upjohn Consumer Healthcare, and Lund University Hospital, Sweden. Lars.Molander@eu.pnu.com
Hansson
A
A
Lunell
E
E
Alainentalo
L
L
Hoffmann
M
M
Larsson
R
R
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003367:Cotinine / Q000097:blood* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000145:classification / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D012720:Severity of Illness Index; D012907:Smoking
D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine