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,...
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doaj-38f8715ebd6348d2b5db3f4da14380c42021-02-22T00:02:11ZengMDPI AGPharmaceutics1999-49232021-02-011328428410.3390/pharmaceutics13020284In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous LesionsMaksim Khotimchenko0Victor Antontsev1Kaushik Chakravarty2Hypatia Hou3Jyotika Varshney4VeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USAVeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USAVeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USAVeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USAVeriSIM Life Inc., 1 Sansome St, Suite 3500, San Francisco, CA 94104, USAThe 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.https://www.mdpi.com/1999-4923/13/2/284computational modelingopioid analgesicstransdermalpharmacokinetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maksim Khotimchenko Victor Antontsev Kaushik Chakravarty Hypatia Hou Jyotika Varshney |
spellingShingle |
Maksim Khotimchenko Victor Antontsev Kaushik Chakravarty Hypatia Hou Jyotika Varshney In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions Pharmaceutics computational modeling opioid analgesics transdermal pharmacokinetics |
author_facet |
Maksim Khotimchenko Victor Antontsev Kaushik Chakravarty Hypatia Hou Jyotika Varshney |
author_sort |
Maksim Khotimchenko |
title |
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions |
title_short |
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions |
title_full |
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions |
title_fullStr |
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions |
title_full_unstemmed |
In Silico Simulation of the Systemic Drug Exposure Following the Topical Application of Opioid Analgesics in Patients with Cutaneous Lesions |
title_sort |
in silico simulation of the systemic drug exposure following the topical application of opioid analgesics in patients with cutaneous lesions |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-02-01 |
description |
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. |
topic |
computational modeling opioid analgesics transdermal pharmacokinetics |
url |
https://www.mdpi.com/1999-4923/13/2/284 |
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