By: 2 May 2016
‘Proliposomal’ local anaesthetic shows promise for longer-lasting pain relief

‘Proliposomal’ local anaesthetic shows promise for longer-lasting pain relief

A new “proliposomal” preparation of the local anaesthetic drug ropivacaine may provide a valuable new option for pain relief in some clinical situations, with key advantages over other types of slow-release local anaesthetics, suggest two reports in Anesthesia & Analgesia.

Proliposomal ropivacaine can deliver long-lasting pain relief with a single injection, with easier preparation and storage than current slow-release local anaesthetic products, according to initial studies in animals and human volunteers. The new formulation was developed and tested by Yehuda Ginosaur of Hadassah Hebrew University Medical Center, Jerusalem, and colleagues.

Liposomal preparations are used as a way of delivering controlled-release of drugs, liposomal local anaesthetics are currently available, but have some important limitations. They are complicated and expensive to manufacture and have a short shelf-life – less than one or two months, even with refrigeration.

To address these shortcomings, Ginosaur and colleagues developed the new “proliposomal” ropivacaine oil. Comparatively easy to prepare, proliposomal ropivacaine oil can be stored at room temperature for up to two years. Liposomes appear, and begin releasing their ropivacaine contents, only when the oil comes into contact with aqueous (water-containing) solutions – including blood plasma.

The researchers initially tested proliposomal ropivacaine in pigs, showing that it gradually released ropivacaine into the animals’ circulation. Ropivacaine levels persisted, along with effective control of pain behaviours, for up to four days after application to a surgical wound.

Ginosaur and colleagues then proceeded to study human volunteers, who were injected with proliposomal or plain ropivacaine at separate locations in the lower back. While the amount injected was the same, the ropivacaine concentration of the proliposomal formulations was eight times higher: four per cent versus 0.5 per cent.

The proliposomal product provided much longer-lasting pain control. Anaesthesia to pinprick pain lasted an average of 29 hours with proliposomal ropivacaine injection, compared to 16 hours with plain ropivacaine. For heat pain, the difference was 36 versus 12 hours.

Peak levels of ropivacaine in the circulation were similar between groups – even though the drug concentration was eight times higher for the proliposomal product. At all times, ropivacaine concentrations remained well below toxic levels.

The prolonged effects of proliposomal ropivacaine – along with its delayed elimination and prolonged redistribution in the circulation – were typical of other types of slow-release local anaesthetic products. “The advantage of this novel proliposomal ropivacaine is its ease of preparation and extended shelf-life stability (>2 years) at room temperature,” Ginosaur and coauthors write.

In an accompanying editorial, Timothy Morey of University of Florida points out the need for further studies to test the advantages of the new proliposomal formulation, especially in clinical situations where its properties may be most useful. For example, proliposomal ropivacaine might be an effective alternative to the use of perineural catheters for repeated local anesthetic injections.

“This is an important advance over existing liposomal preparations, comments Steven Shafer of Stanford University, Editor-in-Chief of Anesthesia & Analgesia. ”Proliposomal products could significantly extend the duration of pain control after infiltration of local anaesthetics—a worthy but so far elusive goal.”

Journal Reference:

  1. Ginosar, Yehuda BSc, MBBS et al. Proliposomal Ropivacaine Oil: Pharmacokinetic and Pharmacodynamic Data After Subcutaneous Administration in Volunteers. Anesthesia & Analgesia, April 2016 DOI:10.1213/ANE.0000000000001217

Source: Wolters Kluwer Health