Comparative Oxycodone Pharmacokinetics in Humans After Intravenous, Oral, and Rectal Administration

Leow, Kim P.; Smith, Maree T.; Watt, J. A.; Williams, Bronwyn; Cramond, Tess

doi:10.1097/00007691-199212000-00008

Cited by 77 publications

(61 citation statements)

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“…Single oral OXY doses used in humans commonly range from 0.07 to 0.38 mg/kg of immediate release formulations. Corresponding peak or early serum OXY concentrations are typically 10 to 100 ng/ml (Leow et al, 1992;Pöyhiä et al, 1992). In the current study, OXY was administered over a comparable dose range of 0.05 to 0.5 mg/kg, but intravenously instead of orally, and produced serum OXY concentrations equaling or exceeding the peak levels from oral dosing in humans.…”

Section: Discussionmentioning

confidence: 99%

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An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

Pravetoni

Naour²,

Harmon

et al. 2012

J Pharmacol Exp Ther

123

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Opioid conjugate vaccines have shown promise in attenuating the behavioral effects of heroin or morphine in animals. The goal of this study was to extend this approach to oxycodone (OXY), a commonly abused prescription opioid. Haptens were generated by adding tetraglycine (Gly) 4 or hemisuccinate (HS) linkers at the 6-position of OXY. Immunization of rats with OXY(Gly) 4 conjugated to the carrier proteins bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) produced high-titer antibodies to OXY and its metabolite oxymorphone with substantially lower affinities for other structurally related opioid agonists and antagonists. There was no measurable binding of antibody by the (Gly) 4 linker alone or off-target opioids methadone and buprenorphine. OXY(HS) conjugates were less immunogenic despite achieving protein haptenation ratios comparable to OXY(Gly) 4 -BSA. In rats given a single intravenous dose of OXY, immunization with OXY(Gly) 4 -KLH increased OXY protein binding and retention in serum while decreasing its unbound (free) concentration in plasma and distribution to brain. Vaccine efficacy correlated with serum antibody titers, and it was greatest in rats given the lowest OXY dose (0.05 mg/kg) but was significant even after a larger OXY dose (0.5 mg/kg), equivalent to the high end of the therapeutic range in humans. These effects of OXY(Gly) 4 -KLH on drug disposition were comparable to those of nicotine or cocaine vaccines that are in clinical trials as addiction treatments. Immunization with OXY(Gly) 4 -KLH also reduced OXY analgesia in a thermal nociception test. These data support further study of vaccination with the OXY(Gly) 4 -KLH immunogen as a potential treatment option for OXY abuse or addiction.

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Section: Discussionmentioning

confidence: 99%

“…The BSA conjugate was used for this experiment because of the ability to verify the haptenation ratio by mass spectrometry. These OXY doses were chosen as representative of the therapeutic single dose range in humans (Leow et al, 1992;Pöyhiä et al, 1992).…”

Section: Oxy(hs)mentioning

confidence: 99%

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

Pravetoni

Naour²,

Harmon

et al. 2012

J Pharmacol Exp Ther

123

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“…The quantifiin about 2 h [ 5,6 ]. Once peak plasma concentrations cation limit of oxycodone in plasma samples was are reached, oxycodone concentrations rapidly decline, 0.2 ng ml−1, with standard curve linearity between with an apparent terminal half-life ranging from 3.0 to 0.2 ng ml−1 and 100 ng ml−1.…”

Section: Introductionmentioning

confidence: 99%

“…Once peak plasma concentrations cation limit of oxycodone in plasma samples was are reached, oxycodone concentrations rapidly decline, 0.2 ng ml−1, with standard curve linearity between with an apparent terminal half-life ranging from 3.0 to 0.2 ng ml−1 and 100 ng ml−1. Inter-day and intra-day 5.7 h [ 5,7]. Because oxycodone is rapidly absorbed precision (expressed as per cent coefficient of variation) and quickly eliminated after oral administration, freranged from 0.4% to 9.9% for nominal standards quent dosing (every 4-6 h) is required to maintain ranging from 0.2 ng ml−1 to 100 ng ml−1.…”

Section: Introductionmentioning

confidence: 99%

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Characterization and validation of a pharmacokinetic model for controlled‐release oxycodone

Mandema

Kaiko²,

Oshlack³

et al. 1996

Brit J Clinical Pharma

135

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1 Oxycodone is a strong opioid agonist that is currently available in immediaterelease ( IR) formulations for the treatment of moderate to severe pain. Recently, controlled-release (CR) oxycodone tablets were developed to provide the benefits of twice-a-day dosing to patients treated with oxycodone. The purpose of this investigation was to develop and validate a pharmacokinetic model for CR oxycodone tablets in comparison with IR oxycodone solution. 2 Twenty-four normal male volunteers were enrolled in a single-dose, randomized, analytically blinded, two-way crossover study designed to compare the pharmacokinetics of two 10 mg CR oxycodone tablets with 20 mg IR oxycodone oral solution. Pharmacokinetic models describing the oxycodone plasma concentration vs time profiles of CR tablets and IR solution were derived using NONMEM version IV. The predictive performance of the models was assessed by comparison of predicted oxycodone plasma concentrations with actual oxycodone plasma concentrations observed in a separate group of 21 volunteers who received repeated doses of IR and CR oxycodone for 4 days. 3 The unit impulse disposition function of oxycodone was best described by a one-compartment model. Absorption rate of the IR solution was best described by a mono-exponential model with a lag time, whereas absorption rate of the CR tablet was best described using a bi-exponential model. The absorption profile of the CR tablets was characterized by a rapid absorption component (t 1/2 abs=37 min) accounting for 38% of the available dose and a slow absorption phase ( t 1/2 abs=6.2 h) accounting for 62% of the available dose. Two 10 mg tablets of oral CR oxycodone hydrochloride were 102.7% bioavailable relative to 20 mg of IR oxycodone hydrochloride oral solution. The population model derived after administration of a single dose accurately predicted both the mean and range of oxycodone concentrations observed during 4 days of repeated dosing. The mean prediction error was 2.7% with a coefficient of variation of 54%. 4 The absorption characteristics of CR oxycodone tablets should allow effective plasma concentrations of oxycodone to be reached quickly and for effective concentrations to be maintained for a longer period after dosing compared with the IR oral solution. The CR dosage form has pharmacokinetic characteristics that permit 12 hourly dosing.

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Single dose oral oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain in adults

Rees

Moore

McQuay

et al. 2000

Cochrane Database of Systematic Reviews

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Comparative Oxycodone Pharmacokinetics in Humans After Intravenous, Oral, and Rectal Administration

Cited by 77 publications

References 0 publications

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

Characterization and validation of a pharmacokinetic model for controlled‐release oxycodone

Single dose oral oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain in adults

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