Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain

Guang-tao, Hao; Zhou, Haiyan; Gao, Han; Qu, Hengyan; Liang, Yumei; Li, Yuanyuan; Dong, Ruihua; Zhang, Lijuan; Wang, Xiaofang; Liu, Zeyuan

doi:10.1016/j.pharep.2013.08.012

Cited by 16 publications

(22 citation statements)

References 23 publications

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“…2004; Hao et al. 2014; Kokubun et al. 2014) and goodness of fit of the two‐compartment analyses of the IV data to assess the intrinsic oxycodone distribution and clearance.…”

Section: Resultsmentioning

confidence: 99%

Slow drug delivery decreased total body clearance and altered bioavailability of immediate‐ and controlled‐release oxycodone formulations

Li¹,

Sun

Palmisano³

et al. 2016

Pharmacology Res & Perspec

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Oxycodone is a commonly used analgesic with a large body of pharmacokinetic data from various immediate‐release or controlled‐release formulations, under different administration routes, and in diverse populations. Longer terminal half‐lives from extravascular administration as compared to IV administration have been attributed to flip‐flop pharmacokinetics with the rate constant of absorption slower than elimination. However, PK parameters from the extravascular studies showed faster absorption than elimination. Sustained release formulations guided by the flip‐flop concept produced mixed outcomes in formulation development and clinical studies. This research aims to develop a mechanistic knowledge of oxycodone ADME, and provide a consistent interpretation of diverging results and insight to guide further extended release development and optimize the clinical use of oxycodone. PK data of oxycodone in human studies were collected from literature and digitized. The PK data were analyzed using a new PK model with Weibull function to describe time‐varying drug releases/ oral absorption, and elimination dependent upon drug input to the portal vein. The new and traditional PK models were coded in NONMEM. Sensitivity analyses were conducted to address the relationship between rates of drug release/absorption and PK profiles plus terminal half‐lives. Traditional PK model could not be applied consistently to describe drug absorption and elimination of oxycodone. Errors were forced on absorption, elimination, or both parameters when IV and PO profiles were fitted separately. The new mechanistic PK model with Weibull function on absorption and slower total body clearance caused by slower absorption adequately describes the complex interplay between oxycodone absorption and elimination in vivo. Terminal phase of oxycodone PK profile was shown to reflect slower total body drug clearance due to slower drug release/absorption from oral formulations. Mechanistic PK models with Weibull absorption functions, and release rate‐dependent saturable total body clearance well described the diverging oxycodone absorption and elimination kinetics in the literature. It showed no actual drug absorption during the terminal phase, but slower drug clearance caused by slower release/absorption producing the appearance of flip‐flop and offered new insight for the development of modified release formulations and clinical use of oxycodone.

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“…2004; Hao et al. 2014; Kokubun et al. 2014) and goodness of fit of the two‐compartment analyses of the IV data to assess the intrinsic oxycodone distribution and clearance.…”

Section: Resultsmentioning

confidence: 99%

Slow drug delivery decreased total body clearance and altered bioavailability of immediate‐ and controlled‐release oxycodone formulations

Li¹,

Sun

Palmisano³

et al. 2016

Pharmacology Res & Perspec

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“…Kim et al [10] demonstrate oxycodone could provide superior analgesia to fentanyl but higher incidence of side effects, including PONV, dizziness, and drowsiness. Hao et al [11] have also shown that side effects of oxycodone hydrochloride include dizziness, nausea, vomiting, drowsiness, and fatigue. For the functional evaluation scores of the 3 groups, group C was the lowest, group A followed, and group B was the highest.…”

Section: Discussionmentioning

confidence: 99%

The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation

et al. 2017

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Background:Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery.Methods:In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking.Results:A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients’ age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 < 90% among the 3 groups, group C's was significantly higher than those of groups A and B, and the difference was statistically significant (P < .05). Group A had no difference compared with group B. In VAS score 30minutes after waking, group C was the highest, followed by group A, with group B as the lowest. The difference among the 3 groups was statistically significant (P < .05), but a difference delta less than 1 on the VAS scale is not clinically significant.Conclusion:The analgesic effect of oxycodone hydrochloride at 0.06 mg/kg applied to painless artificial abortion surgery is not superior than that of fentanyl, but the incidence of intraoperative respiratory depression and hypoxemia is significantly lower than fentanyl.

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“…In a study of 42 Chinese patients who received IV oxycodone in doses of 2.5, 5, or 10 mg, the mean values of C max , AUC 0–6 , and AUC 0–∞ were dose‐dependent, but T max and T 1/2 were not . When patients received 0.5 mg/kg IV oxycodone, the volume of distribution at steady state was 2 to 3 L/kg with a clearance rate of 0.7 to 0.8 L/minute .…”

Section: Oxycodone Pharmacologymentioning

confidence: 99%

“…29,30 Table 1. Mean AUC 0-t ratios of oxycodone IV to metabolites from healthy volunteers in a study over three doses 32 Metabolite to Parent Drug Ratio (Over 3 Doses)…”

Section: Oxycodone Pharmacologymentioning

confidence: 99%

“…31 In a study of 42 Chinese patients who received IV oxycodone in doses of 2.5, 5, or 10 mg, the mean values of C max , AUC 0-6 , and AUC 0-∞ were dose-dependent, but T max and T 1/2 were not. 32 When patients received 0.5 mg/kg IV oxycodone, the volume of distribution at steady state was 2 to 3 L/kg with a clearance rate of 0.7 to 0.8 L/minute. 33 Elimination half-life was 2 to 3 hours following IV oxycodone administration compared to 3 hours for oral oxycodone immediate-release and 4 to 5 hours for oral oxycodone controlled-release formulations.…”

Section: Oxycodone Pharmacologymentioning

confidence: 99%

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Perspectives on Intravenous Oxycodone for Control of Postoperative Pain

et al. 2015

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Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa- as well as mu-opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important "new" old drug for postoperative pain control.

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Pharmacokinetics of oxycodone hydrochloride and three of its metabolites after intravenous administration in Chinese patients with pain

Abstract: Our pharmacokinetics of oxycodone injection in Chinese patients with pain strongly support continued development of oxycodone as an effective analgesic drug in China.

Cited by 16 publications

References 23 publications

Slow drug delivery decreased total body clearance and altered bioavailability of immediate‐ and controlled‐release oxycodone formulations

Slow drug delivery decreased total body clearance and altered bioavailability of immediate‐ and controlled‐release oxycodone formulations

The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation

Perspectives on Intravenous Oxycodone for Control of Postoperative Pain

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