Preclinical and Clinical Pharmacology of Hydrocodone for Chronic Pain: A Mini Review

Abstract

Hydrocodone is one of the most prescribed oral analgesic drugs and it is one of the most abused drugs in general population. It is a mu-opioid agonist predominantly metabolized to the O-demethylated product hydromorphone and to the N-demethylated product norhydrocodone. The purpose of the study is to summarize the preclinical and clinical characteristics of hydrocodone. Pharmacokinetic aspect (terminal half-life, maximum serum concentration, and time to maximum serum concentration) of hydrocodone and the influence of metabolic genetic polymorphism in analgesic response to hydrocodone are also illustrated and commented. Literature on experimental preclinical pharmacology investigating analgesic activity in laboratory animals is furtherly discussed. Moreover, the authors discuss and comment on the updated data regarding safety profile and effectiveness of hydrocodone in the treatment of chronic pain. A bibliographic research was carried out (from February 01, 2018 to August 28, 2018) independently by two researchers (blinded to the authors and initially on results) in the major scientific databases and research engines of peer-reviewed literature on life sciences and biomedical topics, starting from January 1990 to August 2018. Analysis of results of clinical studies suggests that abuse-deterrent extended-release (ER) hydrocodone formulations can be effective and they are well tolerated in the treatment of chronic low back pain. Weaker is the evidence of the analgesic effectiveness of ER hydrocodone on other chronic pain syndromes and non-cancer non-neuropathic chronic pain. In these conditions, hydrocodone showed to have positive effects in non-controlled open studies and needs to be further studied to assess the real strength of results.

Opioids Cause Sex-Specific Vascular Changes via Cofilin-Extracellular Signal-Regulated Kinase Signaling: Female Mice Present Higher Risk of Developing Morphine-Induced Vascular Dysfunction than Male Mice

“…In prior studies, morphine was shown to have a high affinity for the μ-opioid receptor, and low affinities for the δ- and κ-opioid receptors [31]. Similarly, hydrocodone also produces its analgesic effects by activating the μ-opioid receptor but can also stimulate the δ and κ-opioid receptors at high doses [37]. However, hydrocodone is a prodrug that displays only weak binding capacity for the μ-opioid receptor in in vitro experiments [37, 38].…”

“…Similarly, hydrocodone also produces its analgesic effects by activating the μ-opioid receptor but can also stimulate the δ and κ-opioid receptors at high doses [37]. However, hydrocodone is a prodrug that displays only weak binding capacity for the μ-opioid receptor in in vitro experiments [37, 38]. Therefore, when the male cells were exposed to a low concentration of hydrocodone (10 nM), we observed a markedly lower percent confluence over time than that in the cells that were exposed to a higher concentration of the drug (10 μM).…”

Oncologic Approaches for Bone Metastasis Related Pain

“…Bunun yanı sıra majistral olarak hazırlanmaktadır. Hidrokodon yarı sentetik bir opioid türevidir ve tıpkı kodein gibi CYP2D6 aracılığı ile hidromorfona dönüşerek etki gösterir (23).…”

Patient Perceptions and Potential Utility of Pharmacogenetic Testing in Chronic Pain Management and Opioid Use Disorder in the Camden Opioid Research Initiative

“…There is strong evidence that CYP2D6 plays an important role in the metabolism of several commonly prescribed opioid pain medications, including oxycodone [11][12][13][14], codeine [15], tramadol [11,14,16], and hydrocodone [14,17,18]. The product of the CYP2D6 gene, CYP2D6, is the primary enzyme that metabolizes each of these medications into Pharmaceutics 2022, 14, 1863 2 of 12 the active metabolites that provide the majority of analgesia [14].…”

“…The product of the CYP2D6 gene, CYP2D6, is the primary enzyme that metabolizes each of these medications into Pharmaceutics 2022, 14, 1863 2 of 12 the active metabolites that provide the majority of analgesia [14]. Specifically, CYP2D6 metabolizes oxycodone into oxymorphone [11], codeine into morphine [15], tramadol into O-desmethyltramadol [11], and hydrocodone into hydromorphone [18].…”