Disease relevance of Cymidon

• The pharmacokinetics of ketobemidone were not influenced by the addition of a spasmolytic agent in the commercial combination ketobemidone preparation 'Ketogin'. Postoperative pain was relieved in 15 patients by patient-controlled intravenous administration of ketobemidone by means of a programmable drug injector [1].
• The second case describes hyperalgesia occurring after a small dose of sustained-release morphine which disappeared after alternative use of oral ketobemidone [2].
• However, there was no correlation between the elimination of ketobemidone in critically ill patients and plasma C-reactive protein, white blood count or plasma albumin concentrations [3].
• The postoperative use of ketobemidone was higher after uterine leiomyoma embolization (46 mg compared with 12 mg, P<.001) [4].
• In order to ensure sufficient analgesia and avoid toxicity, therapeutic monitoring should be employed when using ketobemidone in this group of patients [3].

High impact information on Cymidon

• Ketobemidone, applied to the spinal cord, equivalent to an intrathecal injection, dose-dependently and selectively reduced C-fibre evoked responses [5].
• Forty patients received the standard postoperative medication, meperidine 1 mg/kg on demand in the recovery room, followed by ketobemidone 5 mg subcutaneously on demand in the surgical ward (on demand (OD) group) [6].
• The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients [1].
• Patient-controlled analgesic therapy, Part III: pharmacokinetics and analgesic plasma concentrations of ketobemidone [1].
• For ketobemidone and meperidine, however, phenyl axial conformations were computed to be only 0.7 and 0.6 kcal/mol higher in energy [7].

Chemical compound and disease context of Cymidon

• The authors report a possible interaction between ketobemidone and busulfan during myeloablative treatment of a patient with acute myeloid leukemia [8].
• Morphine, meperidine and ketobemidone used in continuous i.v. infusion for postoperative pain relief were compared in a double-blind, controlled, prospective study in 81 consecutive consenting adult patients after open-heart surgery, with permission from the hospital ethics committee [9].
• High frequency of cough after intravenous bolus injection of Ketogan (ketobemidone + N,N-dimethyl-3,3-diphenyl-1-methylallylamine chloride) for postoperative pain relief [10].
• Time to first verbal response, pain at rest, postoperative nausea and vomiting, and ketobemidone and dixyrazine utilization were compared [11].

Biological context of Cymidon

• A significant correlation was observed between the glomerular filtration rate (GFR) and the half-life of ketobemidone (r = -0.72, P < 0.05). t1/2,z was generally longer and the variation larger in critically ill patients compared with healthy individuals [3].
• The mean rectal bioavailability for ketobemidone was 44% +/- 9% [12].
• During the study period the patients in the PCA group received more ketobemidone as compared with the NCA group, 61.9+/-24.0 mg and 36.3+/-20.2 mg, respectively (P<0.01) [13].
• However, due to the interindividual variability in plasma levels of ketobemidone, independent of phenotype, individual dosing based on the clinical response and therapeutic drug monitoring is recommended [14].
• Multiple dose kinetics of ketobemidone in surgical patients [15].

Anatomical context of Cymidon

• The first group received intramuscular narcotic analgesic ketobemidone, the second group was given 0.5% bupivacaine-epinephrine intercostal nerve block, and the third group received a single dose of 4 mg of epidural morphine for postoperative pain relief [16].
• The highest observed concentration of ketobemidone in breast milk was 36 ng/ml three hours after administration, and 4-7 hours after administration the concentration was 3-5 fold that in maternal plasma [17].
• If pain relief was not adequate, the infusion rate was doubled, and if this was still not sufficient, 5 mg injections of ketobemidone were given i.v. If the orotracheal tube was not tolerated, the internal branch of the superior laryngeal nerve was blocked [18].
• METHODS: Forty-eight patients randomly received PCA or NCA with ketobemidone following extubation after coronary artery bypass grafting [13].
• In Group I blood loss was replaced with microaggregate-poor erythrocyte concentrate (SAGM-ERC) plus 3% dextran-60 as plasma substitute, and postoperative analgesia was maintained with intramuscular ketobemidone [19].

Associations of Cymidon with other chemical compounds

• In the spinal cord preparation, the activities of ketobemidone and methadone were weaker than in cortex [20].
• Ever since its introduction in 1952, Ketogan has consisted of a combination of the opioid cetobemidone and a spasmolytic drug, A29, in the ratio of 1:5 [21].
• Formation of norketobemidone from ketobemidone was studied and compared with the activities of 11 major CYP enzymes in human liver microsomes [22].
• The opioids methadone, dextropropoxyphene, and ketobemidone are also antagonists at the NMDA receptor [23].
• Oral premedication one hour before minor gynaecological surgery--does it have any effect? A comparison between ketobemidone, lorazepam, propranolol and placebo [24].

Gene context of Cymidon

• Additionally, a good correlation was observed with CYP2C19, CYP2C8 and CYP2B6 at a ketobemidone concentration of 50 microM [22].
• Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein [22].
• The results indicate that the metabolism of ketobemidone is not dependent on CYP2D6 or CYP2C19 [14].
• These data show that the combination of A29 and ketobemidone exert more potent antagonism at the NMDA receptor than does ketobemidone alone [25].

Analytical, diagnostic and therapeutic context of Cymidon

• The mean duration of analgesia after ketobemidone was 5.5 hours, and after intercostal block 11 hours [16].
• Ketobemidone was administered IV via a patient-controlled analgesia pump as a rescue analgesic in all patients [26].
• After iv administration the recovery of unchanged ketobemidone in urine was 13-24%, and after oral administration it was 3-10% [27].
• The 119 patients who had undergone previous Caesarean section lumbar extradural block was administered to 77 (65%); the other 42 (35%) received analgesia with ketobemidone 0.8-1.0 ml i.m. or nitrous oxide in oxygen intermittently, or both [28].
• METHODS: Seventeen patients were studied during their stay in the intensive care unit at Huddinge University Hospital. Nine patients received a single intravenous dose of ketobemidone (0.04 mg kg-1) and eight patients received a single oral dose of 5 mg [3].

References