PMID- 8440766
OWN - NLM
STAT- MEDLINE
DCOM- 19930329
LR  - 20190825
IS  - 0091-2700 (Print)
IS  - 0091-2700 (Linking)
VI  - 33
IP  - 2
DP  - 1993 Feb
TI  - Steady-state pharmacokinetics and dose relationship of nicotine delivered from 
      Nicoderm (Nicotine Transdermal System).
PG  - 161-8
AB  - An open-label, randomized, crossover study determined nicotine pharmacokinetics 
      at steady state of a new Nicotine Transdermal System in 24 healthy adult male 
      smokers. Three doses were each administered for 5 days: 7, 14 and 21 mg nicotine 
      per day. Plasma nicotine concentrations reached steady state by the third day and 
      were sustained throughout the 24-hour application periods. Mean steady-state 
      nicotine and cotinine area under the curve (AUC0-24), maximum plasma 
      concentration (Cmax), minimum plasma concentration (Cmin), average plasma 
      concentration (Cavg), and total urinary cotinine were proportional to the dose of 
      nicotine released in vitro from Nicotine Transdermal System. Time to reach peak 
      concentration (tmax), half-life (t1/2), relative degree of fluctuation (DF) in 
      steady-state plasma nicotine and cotinine concentrations, and renal cotinine 
      clearance were similar for all three dosages, indicating linear pharmacokinetics 
      and no change in nicotine metabolism with increasing dose. Findings from a second 
      study also reflect the linear dose relationship for this Nicotine Transdermal 
      System within the 7 to 21 mg/day dosage range. Bioequivalence based on the 
      confidence interval test was demonstrated for a single application of Nicotine 
      Transdermal System 21 mg/day and the same total dosage achieved by combined 
      administration of Nicotine Transdermal System 7 mg/day plus Nicotine Transdermal 
      System 14 mg/day, although there were small statistical differences. This 
      Nicotine Transdermal System has a well-defined pharmacokinetic profile, with 
      sustained plasma nicotine concentrations, and nicotine pharmacokinetics that are 
      independent of the dose of this Nicotine Transdermal System.
FAU - Gorsline, J
AU  - Gorsline J
AD  - ALZA Corporation, Palo Alto, CA 94303-0802.
FAU - Gupta, S K
AU  - Gupta SK
FAU - Dye, D
AU  - Dye D
FAU - Rolf, C N
AU  - Rolf CN
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 6M3C89ZY6R (Nicotine)
RN  - K5161X06LL (Cotinine)
SB  - IM
MH  - Administration, Cutaneous
MH  - Adult
MH  - Cotinine/blood/pharmacokinetics/urine
MH  - Dose-Response Relationship, Drug
MH  - Half-Life
MH  - Heart Rate/drug effects
MH  - Humans
MH  - Male
MH  - Nicotine/*administration & dosage/*pharmacokinetics
EDAT- 1993/02/01 00:00
MHDA- 1993/02/01 00:01
CRDT- 1993/02/01 00:00
PHST- 1993/02/01 00:00 [pubmed]
PHST- 1993/02/01 00:01 [medline]
PHST- 1993/02/01 00:00 [entrez]
AID - 10.1002/j.1552-4604.1993.tb03938.x [doi]
PST - ppublish
SO  - J Clin Pharmacol. 1993 Feb;33(2):161-8. doi: 10.1002/j.1552-4604.1993.tb03938.x.