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  1. Yusof SR, Abbott NJ, Avdeef A
    Eur J Pharm Sci, 2017 Aug 30;106:274-286.
    PMID: 28614733 DOI: 10.1016/j.ejps.2017.06.016
    Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10-6cm·s-1. The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (pH-MME) analysis of the data indicated a smooth sigmoidal transition from a higher capacity uptake process affecting cationic naloxone (pH5.0-7.0) to a lower capacity uptake process affecting the neutral drug (pH8.0-8.5), with cross-over point near pH7.4. Evidently, measurements at multiple pH values can reveal important information about both cerebrovascular flow and BBB transport kinetics.
    Matched MeSH terms: Oxycodone/pharmacokinetics*
  2. Zin CS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S846-S851.
    PMID: 33828388 DOI: 10.4103/jpbs.JPBS_252_19
    Background: It was reported that opioid consumption in developing countries was stagnated or decreased, but precise data on the consumption are unclear. This study examined the trends and patterns of opioid consumption in Malaysia and other four Southeast Asian countries.

    Materials and Methods: Data of five strong opioids consumption (morphine, oxycodone, fentanyl, pethidine, and methadone) between 2005 and 2014 from Malaysia, Singapore, Indonesia, Thailand, and Vietnam were extracted from the Pain and Policy Studies Group. Defined daily doses per 1000 inhabitants per day (DDD/1000 inhabitants/day) was used for calculating the annual amount of opioid use.

    Results: The total consumption of five strong opioids was increased in all five Southeast Asian countries during a 10-year study period. Malaysia was recorded with the largest increase of the opioid consumption (993.18%), followed by Indonesia (530.34%), Vietnam (170.17%), Singapore (116.16%), and Thailand (104.66%). Malaysia also had the highest total strong opioid consumption (11.2 DDD/1000 inhabitants/day), primarily for methadone. Among the opioids used for pain management, fentanyl was primarily used in Malaysia and Singapore but the greatest increase in these two countries was for oxycodone. Fentanyl was also primarily used in Indonesia while morphine was predominantly used in Thailand and Vietnam.

    Conclusion: Growing trends of strong opioids consumption in all five Southeast Asian countries demonstrated in this study may indicate improved access to opioid analgesics in these countries. Given the increasing trends, it is important to ensure that the utilization of opioids is according to the guideline to prevent the negative consequences of opioids particularly when used in chronic non-cancer pain.

    Matched MeSH terms: Oxycodone
  3. Zin CS, Chen LC, Knaggs RD
    Eur J Pain, 2014 Oct;18(9):1343-51.
    PMID: 24756859 DOI: 10.1002/j.1532-2149.2014.496.x
    BACKGROUND: This study evaluated the prescribing trends of four commonly prescribed strong opioids in primary care and explored utilization in non-cancer and cancer users.
    METHODS: This cross-sectional study was conducted from 2000 to 2010 using the UK Clinical Practice Research Datalink. Prescriptions of buprenorphine, fentanyl, morphine and oxycodone issued to adult patients were included in this study. Opioid prescriptions issued after patients had cancer medical codes were defined as cancer-related use; otherwise, they were considered non-cancer use. Annual number of prescriptions and patients, defined daily dose (DDD/1000 inhabitants/day) and oral morphine equivalent (OMEQ) dose were measured in repeat cross-sectional estimates.
    RESULTS: In total, there were 2,672,022 prescriptions (87.8% for non-cancer) of strong opioids for 178,692 users (59.9% female, 83.9% non-cancer, mean age 67.1 ± 17.0 years) during the study period. The mean annual (DDD/1000 inhabitants/day) was higher in the non-cancer group than in the cancer group for all four opioids; morphine (0.73 ± 0.28 vs. 0.12 ± 0.04), fentanyl (0.46 ± 0.29 vs. 0.06 ± 0.24), oxycodone (0.24 ± 0.19 vs. 0.038 ± 0.028) and buprenorphine (0.23 ± 0.15 vs. 0.008 ± 0.006). The highest proportion of patients were prescribed low opioid doses (OMEQ ≤ 50 mg/day) in both non-cancer (50.3%) and cancer (39.9%) groups, followed by the dose ranks of 51-100 mg/day (26.2% vs. 28.7%), 101-200 mg/day (15.1% vs. 19.2%) and >200 mg/day (8.25% vs. 12.1%).
    CONCLUSIONS: There has been a huge increase in strong opioid prescribing in the United Kingdom, with the majority of prescriptions for non-cancer pain. Morphine was the most frequently prescribed, but the utilization of oxycodone, buprenorphine and fentanyl increased markedly over time.
    Matched MeSH terms: Oxycodone/administration & dosage; Oxycodone/therapeutic use*
  4. Zin CS, Rahman NA, Ismail CR, Choy LW
    Pain Pract, 2017 07;17(6):774-781.
    PMID: 27676695 DOI: 10.1111/papr.12525
    BACKGROUND: There are currently limited data available on the patterns of opioid prescribing in Malaysia. This study investigated the patterns of opioid prescribing and characterized the dosing and duration of opioid use in patients with noncancer and cancer pain.
    METHODS: This retrospective, cross-sectional study was conducted at an outpatient hospital setting in Malaysia. All prescriptions for opioids (dihydrocodeine, fentanyl, morphine, and oxycodone) issued between January 2013 and December 2014 were examined. The number of prescriptions and patients, the distribution of mean daily dose, annual total days covered with opioids, and annual total opioid dose at the individual level were calculated and stratified by noncancer and cancer groups.
    RESULTS: A total of 1015 opioid prescriptions were prescribed for 347 patients from 2013 to 2014. Approximately 41.5% of patients (N = 144/347) and 58.5% (N = 203/347) were associated with noncancer and cancer diagnosis, respectively. Oxycodone (38.0%) was the highest prescribed primarily for the noncancer group. The majority of patients in both noncancer (74.3%) and cancer (60.4%) groups were receiving mean daily doses of < 50 mg morphine equivalents. The chronic use of opioids (> 90 days per year) was associated with 21.8% of patients in the noncancer group and 17.5% in the cancer group.
    CONCLUSIONS: The finding from this study showed that 41.5% of opioid users at an outpatient hospital setting in Malaysia received opioids for noncancer pain and 21.8% of these users were using opioids for longer than 90 days. The average daily dose in the majority of patients in both groups of noncancer and cancer was modest.
    Study site: outpatient clinic, hospital, Malaysia
    Matched MeSH terms: Oxycodone/administration & dosage
  5. Zin CS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S841-S845.
    PMID: 33828387 DOI: 10.4103/jpbs.JPBS_251_19
    Background: Analgesic is commonly used in children but little is known about its patterns of utilization. This study explored the patterns of analgesic prescribing in children.

    Materials and Methods: This cross-sectional study used prescription databases of tertiary hospital settings in Malaysia from 2010 to 2016. Prescriptions for nine NSAIDs (diclofenac, ketoprofen, etoricoxib, celecoxib, ibuprofen, indomethacin, mefenamic acid, meloxicam, and naproxen), tramadol, and five other opioids (morphine, oxycodone, fentanyl, buprenorphine, and dihydrocodeine) prescribed for children aged <18 years were included. Number of annual patients and prescriptions were measured and analyzed using Stata v15.

    Results: During a 7-year study period, a total of 5040 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were prescribed for 2460 pediatric patients (81.8% NSAIDs patients, 17.9% tramadol patients, and 0.3% opioid patients). Ibuprofen was the primary analgesic in young children less than 12 years old (≤2 years old [y.o.] [75%], 3-5 y.o. [85%], and 6-12 y.o. [56.3%]). However, there was a wide range of analgesics used in older children (>12 y.o.) with the majority for naproxen (13-15 y.o. (28.2%) and 16-17 y.o. (28.2%). Other frequently prescribed analgesics for older children included ibuprofen (20.6%) and diclofenac (18.2%) for 12-15 y.o. and diclofenac (26.7%) and tramadol (17.6%) for 16-17 y.o.

    Conclusion: Ibuprofen was the primary analgesic for children less than 12 y.o., whereas there was a wide range of analgesics prescribed for children age >12 y.o. including naproxen, diclofenac, and tramadol.

    Matched MeSH terms: Oxycodone
  6. Galli M, Vergari A, Vitiello R, Nestorini R, Peruzzi M, Chierichini A, et al.
    Malays Orthop J, 2020 Jul;14(2):57-63.
    PMID: 32983378 DOI: 10.5704/MOJ.2007.013
    Introduction: The aim of this study was the evaluation of two different techniques on post-operative analgesia and motor recovery after hallux valgus correction in one-day surgery patients.

    Material and Methods: We enrolled 26 patients scheduled for hallux valgus surgery and treated with the same surgical technique (SCARF osteotomy). After subgluteal sciatic nerve block with a short acting local anaesthetic (Mepivacaine 1.5%, 15ml), each patient received an ultrasound-guided Posterior Tibialis Nerve Block (PTNB) with Levobupivacaine 0.5% (7-8ml). We measured the postoperative intensity of pain using a Visual Analogue Scale (VAS), the consumption of oxycodone after operative treatment and the motor recovery. VAS was detected at baseline (time 0, before the surgery) and at 3, 6, 12 and 24 hours after the operative procedure (T1, T2, T3, T4 respectively). Control group of 26 patients were treated with another post-operative analgesia technique: local infiltration (Local Infiltration Anaesthesia, LIA) with Levobupivacaine 0.5% (15ml) performed by the surgeon.

    Results: PTNB group showed a significant reduction of VAS score from the sixth hour after surgery compared to LIA group (p<0.028 at T2, p<0.05 at T3 and p<0.002 at T4, respectively). Instead, no significant differences were found in terms of post-operative oxycodone consumption and motor recovery after surgery.Conclusions: PTNB resulted in a valid alternative to LIA approach for post-operative pain control due to its better control of post-operative pain along the first 24 hours. In a multimodal pain management according to ERAS protocol, both PTNB and LIA should be considered as clinically effective analgesic techniques.

    Matched MeSH terms: Oxycodone
  7. Zin CS, Nazar NI, Rahman NS, Alias NE, Ahmad WR, Rani NS, et al.
    J Pain Res, 2018;11:1959-1966.
    PMID: 30288090 DOI: 10.2147/JPR.S164774
    Purpose: To examine the trends of analgesic prescribing at public tertiary hospital outpatient settings and explore the patterns of their utilization in nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, and opioid patients.
    Patients and methods: This cross-sectional study was conducted from 2010 to 2016 using the prescription databases of two tertiary hospitals in Malaysia. Prescriptions for nine NSAIDs (ketoprofen, diclofenac, celecoxib, etoricoxib, ibuprofen, indomethacin, meloxicam, mefenamic acid, and naproxen), tramadol, and five other opioids (morphine, fentanyl, oxycodone, dihydrocodeine, and buprenorphine) were included in this study. Annual number of patients and prescriptions were measured in repeat cross-sectional estimates. Descriptive statistics and linear trend analysis were performed using Stata version 13.
    Results: A total of 192,747 analgesic prescriptions of the nine NSAIDs, tramadol, and five other opioids were given for 97,227 patients (51.8% NSAIDs patients, 46.6% tramadol patients, and 1.7% opioid patients) from 2010 to 2016. Tramadol (37.9%, n=72,999) was the most frequently prescribed analgesic, followed by ketoprofen (17.5%, n=33,793), diclofenac (16.2%, n=31,180), celecoxib (12.2%, n=23,487), and other NSAIDs (<4.5%). All the analgesics were increased over time except meloxicam, indomethacin, and mefenamic acid. Opioids, primarily morphine (2.2%, n=4,021) and oxycodone (0.5%, n=1,049), were prescribed the least, but the rate of increase was the highest.
    Conclusion: Tramadol was the most frequently prescribed analgesic in hospital outpatient settings in Malaysia. Opioids were prescribed the least, but noted the highest increase in utilization.
    Data source: Prescription databases of two public tertiary hospitals in Malaysia

    Study site: two public tertiary hospitals in Malaysia
    Matched MeSH terms: Oxycodone
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