Chronic tobacco smoking and gender as variables affecting amantadine disposition in healthy subjects.
Amantadine HCl (3 mg kg-1) was administered orally to 20 young healthy adults. Its apparent volume of distribution (V2/F) was higher in smokers than nonsmokers, 6.05 +/- 0.86 vs 4.87 +/- 0.85 l kg-1; (mean +/- s.d., 10/group, P < 0.011), and no gender-associated effect was observed. Renal clearance did not vary with time-interval, but urinary recovery at 48 h was higher in men than in women (60.2 +/- 7.5% vs 47.0 +/- 15.0%, P < 0.032). Males had higher renal clearances than females when normalised for body mass index (BMI, 0.492 +/- 0.284 vs 0.248 +/- 0.137 l-1 BMI h-1, (10/group, P < 0.032)). On combining data from a previous study, the weight normalised renal clearance was also higher in men than in women, 0.160 +/- 0.075 vs 0.102 +/- 0.053 l kg-1 h-1 (19/group, P < 0.01). Chronic tobacco smoking did not alter the plasma or renal amantadine clearance. We conclude that gender and tobacco smoking are independent variables effecting amantadine disposition.
Wong
L T
LT
Department of Pharmacology, University of Manitoba, Winnipeg, Canada.
Sitar
D S
DS
Aoki
F Y
FY
D000284:Administration, Oral; D000328:Adult; D000547:Amantadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000704:Analysis of Variance; D015992:Body Mass Index; D002849:Chromatography, Gas; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D012727:Sex Characteristics; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*
D000547:Amantadine