Postoperative Pain Management With a Patient-Controlled Transdermal Delivery System for Fentanyl

Peter J. S. Koo

Am J Health Syst Pharm. 2005;62(11):1171-1176.

Pharmacokinetics

The iontophoretic process requires that the hydrochloride salt of fentanyl be used in PCTS. As current flows through the drug-containing anode hydrogel, the fentanyl salt is ionized, and the positively charged fentanyl molecules are repelled from the positively charged anode surface, facilitating fentanyl transport across the skin. Doses delivered from the system are expressed as the amount of ionized fentanyl transferred from the system into the systemic circulation.

When activated, PCTS consistently delivers the preprogrammed 40-µg dose of fentanyl hydrochloride into the systemic circulation at a controlled rate.^[28] The amount of drug delivered is independent of dosage frequency^[29] and is linearly related to the magnitude of the electric current applied to the system: 170 µA delivers a nominal 40-µg dose of fentanyl hydrochloride.^[30]

When healthy volunteers received two sequential 40-µg doses per hour from PCTS for 23.3 hours, the bio-availability of fentanyl delivered increased over time, as approximately 41% of the nominal dose was shown to be absorbed into the systemic circulation after the first hour of treatment and nearly 100% after 10 hours.^[29] This increase is not clinically significant, however, because patients can adjust their own medication to achieve a satisfactory level of pain control. The pharmacokinetics of fentanyl delivered by this system remain consistent over multiple-day administration periods; another trial found no significant differences in the area under the corrected serum concentration-versus-time curve after dosage periods of 20 and 68 consecutive hours ( p = 0.133) ( Table 1 ).^[30] Demographic characteristics (age, body weight, sex, and ethnicity) have also been shown to have no significant pharmacokinetic effect ( Table 2 ).^[31]

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Cite this: Postoperative Pain Management With a Patient-Controlled Transdermal Delivery System for Fentanyl - Medscape - Jun 01, 2005.

Abstract and Introduction
Description
Pharmacokinetics
Pharmacokinetics
Administration
Comparison with Transdermal Fentanyl Patch
Potential Therapeutic Applications
Conclusion
References

Pharmacokinetics of Fentanyl Hydrochloride Delivered by Patient-Controlled Transdermal System After Single- and Multiple-Day Dosing ^a
Pharmacokinetic Variable^b	After One Day ( n = 25)	After Three Days ( n = 25)	p
C _max (µg/L)	0.30	0.48	0.0001
t _max (hr)	1.66	1.33	--
t (hr)	11.4	14.2	0.0001
AUC_0-5 (µg•hr/L)	1.20	1.88	0.0001
C _pre (µg/L)	0.21	0.34	0.0001
Corrected AUC_0-5 (µg•hr/L)	0.40	0.54	0.133

^aAdapted from reference 30, with permission.

^b C _max = maximum concentration; t _max = time to C _max; t = half-life; AUC_0-5 = area under the concentration-versus- time curve from zero to five hours; C _pre = predose concentration.

Effect of Subject Demographics on AUC _0-∞ ^a
Demographic Characteristic	n	Least-Squares Mean ± S.E.	Mean ± S.E. Difference	95% Confidence Interval	p
Race			-0.300 ± 1.560	-3.428 to 2.828	0.848
Black	28	2.98 ± 0.92
White	36	3.28 ± 1.08
Age (yr)			1.447 ± 1.467	-1.495 to 4.389	0.328
18-45	39	3.85 ± 0.75
>65	25	2.41 ± 1.15
Build			1.140 ± 1.279	-1.425 to 3.705	0.377
Lean	31	3.70 ± 0.98
Obese	33	2.56 ± 0.81
Sex			1.201 ± 1.577	-1.963 to 4.364	0.450
Female	27	3.73 ± 1.03
Male	37	2.53 ± 0.99

^aReproduced from reference 31, with permission. AUC_0-∞= area under the concentration-versus-time curve from zero hours to infinity.

Table 3. Secondary Efficacy Endpoints for Largest Placebo-Controlled Studies Comparing Fentanyl Hydrochloride Patient-Controlled Transdermal System (PCTS) With Placebo ^a
Endpoint	PCTS ( n = 235)	Placebo ( n = 204)	p
No. pts. withdrawing from study for any reason (%)	81 (34.5)	128 (62.7)	<0.0001
No. pts. with successful pain control (%)^b
PGA	179 (76.2)	106 (52.0)	<0.0001
IGA	176 (74.9)	107 (52.5)	<0.0001

^aData on file, ALZA Corp., Mountain View, CA, protocol C2001-011.

^bSuccessful pain control = a rating of pain control as excellent or good. PGA = patient global assessment, IGA = investigator global assessment.

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