A novel transdermal formulation of fentanyl-containing dipropylene glycol droplets dispersed in a silicone matrix with a rate-controlling membrane was developed. Healthy male subjects (n = 24) received repeated 72-hour applications of fentanyl (50 mug/h) as the novel matrix and the conventional reservoir formulations in a randomized, 2-way crossover study. Blood samples were collected, and serum concentrations of fentanyl were assayed using liquid chromatography with mass spectrometry detection. The mean area under the curve (AUCtau) and peak concentrations (C(max)) of the matrix formulation were 84 838 pg.h/mL and 1680 pg/mL, respectively. Ratio and 90% confidence intervals of AUCtau and C(max) between the 2 formulations were within 80% to 125%. Adherence of the matrix formulation was higher than the reservoir formulation (62.5 vs 56.2%, P < .0001), without affecting skin irritation. Vital signs and adverse events of the 2 formulations were similar in nature and frequency. The novel matrix formulation displayed enhanced adherence and resulted in similar pharmacokinetics and tolerability as the reservoir formulation.

AimTo determine the pharmacokinetics, safety and performance of a novel matrix formulation of fentanyl. MethodsTransdermal fentanyl was administered as the novel matrix and the Durogesic ® reservoir formulations (24 subjects, 100 µ g h − 1 ) in a randomized, fully replicate, fourway crossover study. Serum concentrations of fentanyl were assayed by LC/MS/MS. Pharmacokinetic parameters of fentanyl and performance (adherence and skin irritability) were evaluated. ResultsTest/reference ratio (90% confidence intervals) for AUC 0-t , AUC inf and C max were 105.5% (99.4, 112.0), 105.3% (99.3, 111.6) and 111.4% (100.4, 123.6), respectively. Adherence and skin irritability results of the two formulations were similar. ConclusionThe two formulations are expected to result in similar efficacy for the management of severe pain.

Background/Aims Recommended initial dose of fentanyl (FEN) in opioid‐naive patients is 25μg/h with upward titration. The aim was to assess the pharmacokinetics (PK), safety and tolerability of a FEN patch given with naltrexone (NAL), an opioid receptor antagonist. Methods In a randomized crossover study, healthy male subjects (n=24) received a single 72h application of two formulations of FEN (100μg/h) given with oral NAL (100mg) in a clinical setting. Blood samples were collected and serum FEN was assayed using a LC/MS/MS method. Results Mean (CV%) for AUC and Cmax were 142.7ng·h/mL (25.0) and 2.35ng/mL (34.8), respectively. PK parameters of FEN were similar for the reference product with and without NAL. Even though a high dose of FEN was administered, oral NAL prevented the occurrence of opioid adverse events (AEs). Of the 281 AEs, 139 were drug‐related with 100 specific to the patch application site. Most AEs were mild and none were severe. Conclusions Co‐administration of oral NAL did not affect the PK of FEN and prevented the occurrence of opioid AEs. Results from this study confirm that a 100μg/h dose of FEN was well tolerated and safe when given with NAL in healthy males. Clinical Pharmacology & Therapeutics (2005) 77, P76–P76; doi: