Bioavailability of oxycodone by mouth in coronary artery bypass surgery patients – a randomized trial

Valtola, Antti; Morse, James D.; Florkiewicz, Pawel; Hautajärvi, Heidi; Lahtinen, Pasi; Musialowicz, Tadeusz; Anderson, Brian J.; Ranta, Veli‐Pekka; Kokki, Hannu

doi:10.1080/21556660.2020.1797753

Cited by 6 publications

(8 citation statements)

References 32 publications

(69 reference statements)

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“…Absorption of nasogastric elixir paracetamol in adults undergoing cardiac surgery was delayed compared with healthy adults [ 42 ]. The absorption of oral oxycodone is also delayed after cardiac surgery, with the most profound delay (when compared with preoperative administration) observed on the first postoperative day [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers

Morse

Stănescu

Atkinson

et al. 2022

Eur J Drug Metab Pharmacokinet

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Background and Objective Combined acetaminophen and ibuprofen are common antipyretic and analgesic drugs. Formulation and feeding affect drug absorption. Drug clearance has a nonlinear relationship with total body weight. The covariate effect of fat mass on acetaminophen and ibuprofen pharmacokinetics remains unexplored. This study sought to quantify acetaminophen and ibuprofen pharmacokinetics with intravenous, tablet, sachet and oral suspension formulations in fed and fasted states. Methods Pooled time–concentration data for acetaminophen and ibuprofen were available from fasting and fed healthy adults. Data from intravenous, tablet, sachet and suspension formulations were analysed using nonlinear mixed-effects models. Body composition was considered as a covariate on clearances and volumes of distribution ( V d ). Size metrics investigated were total body weight, fat and fat-free mass. Theory-based allometry was used to scale pharmacokinetic parameters to a 70 kg individual. A factor on absorption half-life and lag time quantified delays due to feeding for oral formulations. Pharmacokinetic-pharmacodynamic simulations were used to explore the time courses of pain response for acetaminophen and ibuprofen for each formulation. Results Pooled data included 116 individuals (18–49 years, 49–116 kg) with 6095 acetaminophen and 6046 ibuprofen concentrations available for analysis. A two-compartment pharmacokinetic model with first-order elimination described disposition for both drugs. Normal fat mass was the best covariate to describe acetaminophen clearance (CL), with a factor for fat contribution (FFATCL) of 0.816. Acetaminophen volume of distribution was described using total body weight. Normal fat mass was the best covariate to describe ibuprofen clearance (FFATCL = 0.863) and volume of distribution: (FFATV = 0.718). Clearance and central volume of distribution were 24.0 L/h/70 kg and 43.5 L/h/70 kg for acetaminophen. Ibuprofen clearance and central volume of distribution were 3.79 L/h/70 kg and 10.5 L/h/70 kg. Bioavailability and absorption half-life were 86% and 12 min for acetaminophen and 94% and 27 min for ibuprofen. Absorption lag times were 5.3 min and 6.7 min for acetaminophen and ibuprofen, respectively. Feeding increased both absorption half-life and absorption lag time when compared to the tablet formulation under fasting conditions. Feeding had the most pronounced effect on the lag time associated with tablet formulation for both drugs. Time to a pain score reduction of 2 points (visual analogue score, 0–10) differed by only 5–10 min across all formulations for acetaminophen and ibuprofen. Conclusion Fat mass was an important covariate to describe acetaminophen and ibuprofen pharmacokinetics. The absorption half-lives of acetaminophen and ibuprofen were increased in fed states. The delay in absorption, quantified by a lag time, was protracted for both dru...

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers

Morse

Stănescu

Atkinson

et al. 2022

Eur J Drug Metab Pharmacokinet

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“…This semi-synthetic opioid is stronger than morphine [40]. It is absorbed mainly in the small intestine [41]. Szałek et al, conducted a study on the pharmacokinetics of oxycodone in patients after total gastrectomy.…”

Section: Analgesic Drugsmentioning

confidence: 99%

The Effects of Bariatric Surgery and Gastrectomy on the Absorption of Drugs, Vitamins, and Mineral Elements

2021

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Bariatric surgery, which is an effective treatment for obesity, and gastrectomy, which is the primary treatment method for gastric cancer, alter the anatomy and physiology of the digestive system. Weight loss and changes in the gastrointestinal tract may affect the pharmacokinetic parameters of oral medications. Both bariatric and cancer patients use drugs chronically or temporarily. It is important to know how surgery affects their pharmacokinetics to ensure an effective and safe therapy. The Cochrane, PubMed, and Scopus databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. Studies show that bariatric surgery and gastrectomy most often reduce the time to maximum plasma concentration (tmax) and decrease the maximum plasma concentration (Cmax) in comparison with the values of these parameters measured in healthy volunteers. Vitamin and mineral deficiencies are also observed. The effect depends on the type of surgery and the properties of the drug. It is recommended to use the drugs that have been tested on these groups of patients as it is possible to monitor them.

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“…Chemically, oxycodone is a weak base with a p K a value of 8.53 7 . It is moderately protein bound in plasma (38‐45%) and has oral bioavailability of 40‐70% 8–11 . Previously, Seaton et al 12 found oxycodone to be excreted into human breast milk during the first 72 h after Caesarean delivery.…”

Section: Introductionmentioning

confidence: 99%

“…7 It is moderately protein bound in plasma (38-45%) and has oral bioavailability of 40-70%. [8][9][10][11] Previously, Seaton et al 12 found oxycodone to be excreted into human breast milk during the first 72 h after Caesarean delivery. The highest oxycodone concentrations in breast milk were >100 ng/mL and neonatal exposure was up to 10% of a therapeutic infant dose through ingestion.…”

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confidence: 99%

Breast milk oxycodone concentrations in mothers given oxycodone for post‐Caesarean delivery pain management

Pesonen,

Hakomäki,

Kokki

et al. 2024

Brit J Clinical Pharma

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AimsBoth effective analgesia and early breastfeeding play an important role in maternal and neonatal well‐being after Caesarean delivery. We studied controlled‐release oxycodone tablet treatment for postoperative pain management and determined the excretion of oxycodone into breast milk.MethodsControlled‐release oxycodone/naloxone 10/5‐mg tablets (n = 21) or controlled‐release oxycodone 10‐mg tablets (n = 22) were administered to mothers twice a day for the first 3 days after elective Caesarean delivery as a part of multimodal analgesia. Maternal plasma and breast milk samples were collected daily. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed with ultra‐performance liquid chromatography‐mass spectrometry. Maternal pain intensity was recorded with an 11‐point Numeric Rating Scale (0‐10). Neonatal oxycodone exposure was estimated by simulating five different exposure scenarios, including the highest possible exposure through breast milk.ResultsThe mean oxycodone and noroxycodone milk‐to‐maternal plasma ratios were 3.2 and 3.0, respectively. A strong correlation was found between plasma and breast milk oxycodone (R2 = 0.87) and noroxycodone concentrations (R2 = 0.91). In the simulated highest neonatal exposure scenario, the neonate's maximum plasma concentration was estimated to be 5.4 ng/mL and the estimated weight‐adjusted infant oxycodone dose was less than 10% of the maternal dose. Pain intensities were similarly low between the two treatment groups.ConclusionsThe oxycodone dose received from colostrum and breast milk during the first three postoperative days after Caesarean delivery is assumed safe for healthy, term neonates, but in extreme cases it is possible for the neonate to receive a dose through breast milk that may elicit opioid effects.

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Bioavailability of oxycodone by mouth in coronary artery bypass surgery patients – a randomized trial

Cited by 6 publications

References 32 publications

Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers

Population Pharmacokinetic Modelling of Acetaminophen and Ibuprofen: the Influence of Body Composition, Formulation and Feeding in Healthy Adult Volunteers

The Effects of Bariatric Surgery and Gastrectomy on the Absorption of Drugs, Vitamins, and Mineral Elements

Breast milk oxycodone concentrations in mothers given oxycodone for post‐Caesarean delivery pain management

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