Bioanalytical methods for the quantification of hydromorphone, fentanyl, norfentanyl, morphine, morphine-3ß-glucuronide and morphine-6ß-glucuronide in human plasma

Bruijn, Peter de; Kuip, Evelien; Lam, Mei-Ho; Mathijssen, Ron H.J.; Koolen, Stijn L.W.

doi:10.1016/j.jpba.2017.11.035

Cited by 9 publications

(2 citation statements)

References 18 publications

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“…Plasma was transferred into polypropylene tubes (1.8 mL Nunc vials), which was stored at T < −70 °C (T < −20 °C during collection period) until the time of analysis. Fentanyl in plasma was quantitated using a validated UPLC-MS/MS method [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Kuip

Oldenmenger

Hoop

et al. 2018

Cancers

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Over 90% of patients treated for head and neck cancer with curatively aimed chemo or bioradiotherapy will develop painful mucositis and xerostomia. Sublingually delivered fentanyl (SDL) is a rapid acting opioid to treat breakthrough pain. It is unclear how SDL is absorbed by the mucosa of these patients. Therefore, the aim of this study was to investigate the effects of mucositis and xerostomia on the absorption of SDL. Thirteen patients who received chemo or bioradiotherapy (RT), were given a single dose of fentanyl: Before start of RT, 3 and 6 weeks after start of RT, and 6 weeks after finishing RT. Pharmacokinetic samples were taken. The primary endpoint was the relative difference (RD) between systemic exposure to fentanyl (area under the curve; AUC) at baseline (AUCbaseline) and fentanyl AUC in the presence of mucositis grade ≥2. The secondary endpoint was the RD between AUCbaseline and fentanyl AUC in the presence of xerostomia, which were analyzed by means of a paired t-test on log-transformed data. Mucositis resulted in a 12.7% higher AUC (n = 13; 95% CI: −10.7% to +42.2%, p = 0.29) compared to baseline levels and xerostomia resulted in a 22.4% lower AUC (n = 8; 95% CI: −51.9% to +25.3%, p = 0.25) compared to baseline levels. Mucositis grade ≥2 or xerostomia caused by chemo or bioradiotherapy does not significantly alter the systemic exposure to SDL. Patients with pain during and after chemo or bioradiotherapy may be safely treated with SDL.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Kuip

Oldenmenger

Hoop

et al. 2018

Cancers

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“…Therefore, we obtained 19 CSF patient samples (age range: 0-11 months postnatal age, median 3 days postnatal age), which were collected in the setting of clinical care and stored in the Radboudumc CSF Biobank, Nijmegen, Netherlands. Morphine concentrations were determined using LC-MS/MS quantification methods as described previously by de Bruijn et al [90]. Age and individual dosing regimens were extracted from the electronic patient records to allow patient-specific simulations.…”

Section: Clinical Data For Model Validationmentioning

confidence: 99%

Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children

Verscheijden

Litjens²,

Koenderink

et al. 2021

PLoS Comput Biol

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Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. Age-dependent brain disposition of morphine could contribute to this variability, as developmental increase in blood-brain barrier (BBB) P-glycoprotein (Pgp) expression has been reported. In addition, age-related pharmacodynamics might also explain the variability in effect. To assess the influence of these processes on morphine effectiveness, a multi-compartment brain physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) model was developed in R (Version 3.6.2). Active Pgp-mediated morphine transport was measured in MDCKII-Pgp cells grown on transwell filters and translated by an in vitro-in vivo extrapolation approach, which included developmental Pgp expression. Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature. Model simulations after single dose morphine were compared with measured and published concentrations of morphine and M6G in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), as well as published drug responses in children (1 day– 16 years) and adults. Visual predictive checks indicated acceptable overlays between simulated and measured morphine and M6G concentration-time profiles and prediction errors were between 1 and -1. Incorporation of active Pgp-mediated BBB transport into the PB-PK/PD model resulted in a 1.3-fold reduced brain exposure in adults, indicating only a modest contribution on brain disposition. Analgesic effect-time profiles could be described reasonably well for older children and adults, but were largely underpredicted for neonates. In summary, an age-appropriate morphine PB-PK/PD model was developed for the prediction of brain pharmacokinetics and analgesic effects. In the neonatal population, pharmacodynamic characteristics, but not brain drug disposition, appear to be altered compared to adults and older children, which may explain the reported differences in analgesic effect.

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Opioid responsiveness of nociceptive versus mixed pain in clinical cancer patients

Bechakra

Moerdijk

Rosmalen

et al. 2018

European Journal of Cancer

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Bioanalytical methods for the quantification of hydromorphone, fentanyl, norfentanyl, morphine, morphine-3ß-glucuronide and morphine-6ß-glucuronide in human plasma

Cited by 9 publications

References 18 publications

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy

Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children

Opioid responsiveness of nociceptive versus mixed pain in clinical cancer patients

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