Sex differences in responsiveness to the prescription opioid oxycodone in mice

Collins, Devon T.; Reed, Brian; Zhang, Yong; Kreek, Mary Jeanne

doi:10.1016/j.pbb.2016.06.006

Cited by 52 publications

(51 citation statements)

References 46 publications

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“…23 Contradictory results regarding a correlation between opioid potency and gender exist. [34][35][36][37][38][39] In most animal studies, morphine and oxycodone had a higher potency in males compared to females. 36,38 Kim et al found higher pain relief in men compared to females after equivalent oxycodone dosages.…”

Section: Cns Effectsmentioning

confidence: 99%

“…[34][35][36][37][38][39] In most animal studies, morphine and oxycodone had a higher potency in males compared to females. 36,38 Kim et al found higher pain relief in men compared to females after equivalent oxycodone dosages. 39 In contrast, human males have been found to require 30%-40% more morphine to obtain similar analgesic effects compared to females.…”

Section: Cns Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Population pharmacokinetic‐pharmacodynamic modelling of liquid and controlled‐release formulations of oxycodone in healthy volunteers

Ladebo

Foster

Abuhelwa

et al. 2019

Basic Clin Pharma Tox

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Oral controlled‐release formulations are playing an ever‐increasing role in opioid therapy; however, little is known about their influence on the relationship between pharmacokinetics and pharmacodynamics. The study aim was to characterize the pharmacokinetic‐pharmacodynamics of two controlled‐release tablet formulations and a liquid formulation of oxycodone in healthy, opioid‐naïve volunteers, which can serve as a reference for future patient studies. A semi‐double‐blinded, three‐way crossover study was conducted, with fifteen healthy volunteers receiving two differently designed 20 mg monophasic controlled‐release oxycodone tablets and 10 mg oral solution oxycodone in a randomized order. Venous plasma concentrations and pupil diameter were determined pre‐dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.33, 2.66, 3, 3.33, 3.66, 4, 5, 6, 8, 12 and 24 hour post‐dose. Oxycodone pharmacokinetics was best described by a two‐compartment model with first‐order absorption. The controlled‐release formulations had an absorption lag of 0.23 hour and a slower absorption rate constant (kaCR = 0.19 hour‐1) compared to the oral solution (kaSOL = 0.94 hour‐1). Effects on pupil diameter were delayed relative to plasma (14 minutes half‐life) for all formulations and were best described by a proportional Emax model. The plasma concentration of oxycodone at half‐maximum effect was lower in males (31.1 μg/L) compared to females (52.8 μg/L; P < .001). The absorption profile of controlled‐release oxycodone formulations provided a prolonged onset and offset of action compared to oral solution oxycodone. The controlled‐release formulations showed no differences in pharmacokinetic and pharmacodynamic parameters suggesting that both may be used interchangeably in human beings with normal gastrointestinal function.

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Section: Cns Effectsmentioning

confidence: 99%

Section: Cns Effectsmentioning

confidence: 99%

Population pharmacokinetic‐pharmacodynamic modelling of liquid and controlled‐release formulations of oxycodone in healthy volunteers

Ladebo

Foster

Abuhelwa

et al. 2019

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…Furthermore, pain perception might differ between species, between lines and strains, and between sexes, and also depends on the age of the animal [12][13][14][15] . In addition, possible sex differences in drug biotransformation and pharmacokinetics have been discussed 16 .…”

Section: Effect Of Analgesia Protocolsmentioning

confidence: 99%

Side effects of pain and analgesia in animal experimentation

Jirkof

2017

Lab Anim

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“…Recent data suggests females are more likely to orally consume prescription opioids than use other routes of administration and women advance to regular prescription opioid use more quickly than males (Back, Lawson, Singleton et al, 2011;Gasior, Bond & Malamut, 2016;Kirsh, Peppin & Coleman, 2012). In rodent models, females show elevated oxycodone-induced locomotion (Collins, Reed, Zhang et al, 2016) and intravenous self-administration compared with males (Mavrikaki, Pravetoni, Page et al, 2017). While it is thought that sex hormones at least partially regulates drug-seeking behavior (Lynch, Roth & Carroll, 2002), it is unknown whether sex differences exist in oral oxycodone self-administration and if these potential differences are regulated by sex hormones.…”

Section: Introductionmentioning

confidence: 99%

Oral prescription opioid-seeking behavior in male and female mice

Phillips¹,

McGovern²,

Lee³

et al. 2019

Preprint

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A significant portion of prescription opioid users self-administer orally rather than intravenously. Animal models of opioid addiction have demonstrated that intravenous cues are sufficient to cause drug-seeking. However, intravenous models may not model oral users, and the preference to self-administer orally appears to be partially influenced by the user's sex. Our objectives were to determine whether oral opioid-associated cues are sufficient for relapse and whether sex differences exist in relapse susceptibility. Mice orally selfadministered escalating doses of oxycodone under postprandial (prefed) or non-postprandial (no prefeeding) conditions. Both sexes demonstrated robust cue-induced reinstatement. In separate mice we found that oral oxycodone cues were sufficient to reinstate extinguished oral oxycodone-seeking behavior in the absence of postprandial or prior water self-administration training. During self-administration, we found that female mice earned significantly more mg/kg oxycodone than male mice. Follow-up studies indicated sex differences in psychomotor stimulation and plasma oxycodone/oxymorphone following oral oxycodone administration. In addition, gonadal steroid studies were performed in which we found divergent responses where ovariectomy enhanced and orchiectomy suppressed oral self-administration. While the suppressive effects of orchiectomy were identified across doses and postprandial conditions, the enhancing effects of ovariectomy were selective to non-postprandial conditions. These studies establish that 1) oral drug cues are sufficient to cause reinstatement that is independent of prandial conditions and water-seeking behavior, 2) earned oral oxycodone is larger in female mice compared with male mice potentially through differences in psychomotor stimulation and drug metabolism, and 3) gonadectomy produces divergent effects on oral oxycodone self-administration between sexes.

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Sex differences in responsiveness to the prescription opioid oxycodone in mice

Cited by 52 publications

References 46 publications

Population pharmacokinetic‐pharmacodynamic modelling of liquid and controlled‐release formulations of oxycodone in healthy volunteers

Population pharmacokinetic‐pharmacodynamic modelling of liquid and controlled‐release formulations of oxycodone in healthy volunteers

Side effects of pain and analgesia in animal experimentation

Oral prescription opioid-seeking behavior in male and female mice

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