In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions

The use of opioid analgesics in treating severe pain is frequently associated with putative adverse effects in humans. Topical agents that are shown to have high efficacy with a favorable safety profile in clinical settings are great alternatives for pain management of multimodal analgesia. However, the risk of side effects induced by transdermal absorption and systemic exposure is of great concern as they are challenging to predict. The present study aimed to use BIOiSIM an artificial intelligence-integrated biosimulation platform to predict the transdermal disposition of opioid analgesics. The model successfully predicted their exposure following the topical application of central opioid agonist buprenorphine and peripheral agonist oxycodone in healthy human subjects with simulation of intra-skin exposure in subjects with burns and pressure wounds. The predicted plasma levels of analgesics were used to evaluate the safety of the therapeutic pain control in patients with the dermal structural impairments caused by acute (burns) or chronic cutaneous lesions (pressure wounds) with topical opioid analgesics.

Automated summary

The study successfully predicted the transdermal disposition of opioid analgesics in human subjects using an artificial intelligence-integrated biosimulation platform, and evaluated the safety of using these drugs in patients with skin injuries through the predicted plasma levels of the analgesics.