Effects of application site and subject demographics on the pharmacokinetics of fentanyl HCl patient-controlled transdermal system (PCTS).
BACKGROUND
The fentanyl HCl patient-controlled transdermal system (PCTS) is a self-contained, preprogrammed, needle-free system currently in development for acute pain management in a medically supervised setting. The objectives of these studies were to evaluate skin application sites for the fentanyl HCl PCTS and to evaluate the effect of patient demographics on its pharmacokinetics.


METHODS
The first study was a randomised, open-label, single-centre, 3-treatment, crossover study in which the fentanyl HCl PCTS was applied to the upper outer arm, lower inner arm or chest of healthy volunteers. Fentanyl 25 microg was then delivered via this system twice during the first 20 minutes of every hour for 24 hours. The pharmacokinetics of fentanyl were determined and analysed for each application site using ANOVA. The second study was a nonrandomised, nonblind, multicentre, sequential treatment study. Healthy volunteers received fentanyl HCl 40 microg via the PCTS three times during the first 30 minutes of each hour for 3 hours. After a 5- to 10-day washout period, fentanyl HCl 120 microg was administered intravenously during the first 30 minutes of each hour for 3 hours as a reference treatment. Pharmacokinetic parameters were determined for the fentanyl HCl PCTS, and results were analysed using ANOVA. Safety and tolerability were evaluated in both studies.


RESULTS
Application of the system to the upper outer arm or chest resulted in similar maximum serum concentrations (Cmax; 1.193 and 1.176 microg/L, respectively) and areas under the serum concentration-time curve (AUC24-25; 1.033 and 1.015 microg h/L). However, both Cmax and AUC24-25 were less when the system was applied to the lower inner arm (0.859 microg/L and 0.757 microg x h/L). Subject age, bodyweight, sex and ethnicity had no significant effect on pharmacokinetic parameters. No serious adverse events were reported in either study during or after administration of the fentanyl HCl PCTS.


CONCLUSIONS
Fentanyl HCl is comparably absorbed from the PCTS when it is applied to the upper outer arm or chest. The pharmacokinetics of fentanyl HCl delivered by the PCTS are unaffected by sex, age, race or weight.
Gupta
Suneel K
SK
ALZA Corporation, Mountain View, California 94043, USA.
Hwang
Stephen
S
Southam
Mary
M
Sathyan
Gayatri
G
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001835:Body Weight / Q000502:physiology; D018592:Cross-Over Studies; D003710:Demography; D005006:Ethnicity; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
D000701:Analgesics, Opioid; D005283:Fentanyl