Pharmacokinetics, safety and tolerability of a novel 100 ?g/h transdermal fentanyl patch co-administered with 100 mg oral naltrexone in healthy males

Abstract

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:

Safety, Tolerability, and Dose Proportionality of a Novel Transdermal Fentanyl Matrix Patch and Bioequivalence With a Matrix Fentanyl Patch: Two Phase 1 Single‐Center Open‐Label, Randomized Crossover Studies in Healthy Japanese Volunteers

“…To prevent adverse drug reactions and prevent the emergence of symptoms associated with fentanyl use, the opioid antagonist naltrexone was administered in a dose regimen proven to be safe in healthy volunteers. 21,22 Both studies were conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Study 1 was approved by the Plymouth Independent Ethics Committee (Plymouth, Devon, UK) in 2011; study 2 was approved by the National Health Service National Research Ethics Service London-Surrey borders (London, UK) in 2011.…”

“…To prevent adverse drug reactions and prevent the emergence of symptoms associated with fentanyl use, the opioid antagonist naltrexone was administered in a dose regimen proven to be safe in healthy volunteers 21,22 . Both studies were conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.…”