Metabolized in the liver by CYP 2D6 into an active metabolite, dihydromorphine, and by CYP 3A4 into secondary primary metabolite, nordihydrocodeine. A third primary metabolite is dihydrocodeine-6-glucuronide. [1] The time for mean peak concentration in acid metabolites is 1.76h and 1.98h for a 30 and 60mg dose, respectively. The concentrations achieved were 563 ug/1 and 1476 ug/1, respectively. [2]
来源:DrugBank
代谢
双氢可待因已知的人类代谢物包括去甲双氢可待因和对甲吗啡。
Dihydrocodeine has known human metabolites that include Desmethyl dihydrocodeine and Paramorfan.
◉ Summary of Use during Lactation:Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, and severe central nervous system depression. Like codeine, pharmacogenetics probably plays a role in the extent of central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Dihydrocodeine possibly caused severe respiratory depression in one newborn infant whose mother was taking the drug for cough. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of hydromorphone to 2 to 3 days at a low dosage with close infant monitoring. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Because there is little published experience with dihydrocodeine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants:A woman began taking dihydrocodeine drops for cough twice daily (5.28 mg) beginning on the first day postpartum. One day later, her breastfed infant was difficult to arouse and was not breastfeeding well. The infant had bradycardia, hypoglycemia, and an oxygen saturation of 85%. After 24 hours in the hospital, all symptoms resolved. The symptoms were possibly caused by dihydrocodeine in milk.
◉ Effects on Lactation and Breastmilk:Narcotics can increase serum prolactin. However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Bioavailability is low (approximately 20%) if administered orally. This may be due to poor gastrointestinal absorption. It is also likely due to pre-systemic metabolism by the liver and intestinal wall. [2] The AUCs after oral and intravenous administration are similar (3203ug/l/h and 3401ug/l/h, respectively). [2] Time to peak values are 1.6 and 1.8hours for a 30mg and 60mg dose, respectively. The concentrations achieved were 71.8 ug/1 and 146 ug/1, respectively. [2]
来源:DrugBank
吸收、分配和排泄
消除途径
肾脏消除和尿液排泄。
Renal elimination and urinary excretion. [1]
来源:DrugBank
吸收、分配和排泄
分布容积
二氢可待因的处置被描述为双室模型。
The disposition of dihydrocodeine is described as a two compartment model. [2]
Plasma clearance is approximately 300ml/min. [2] The pharmacokinetics of dihydrocodeine and active metabolite dihydromorphine have been reported to be linear. [1] The decline in plasma dihydrocodeine concentrations after intravenous administration has been described as bi-exponential, with a sleep decline in the initial 2h following administration, followed by a mono-exponential decline thereafter. Clearance was not dose dependent. [2]
[EN] PROCESS FOR REDUCING THE 6-KETO GROUP OF A MORPHINAN ALKALOID TO THE 6-HYDROXY GROUP BY HYDROGENATION [FR] PROCÉDÉ DE RÉDUCTION DU GROUPE 6-CÉTO D'UN ALCALOÏDE DE MORPHINANE EN GROUPE 6-HYDROXY PAR HYDROGÉNATION
[EN] IMIDAZOLIUM REAGENT FOR MASS SPECTROMETRY<br/>[FR] RÉACTIF D'IMIDAZOLIUM POUR SPECTROMÉTRIE DE MASSE
申请人：HOFFMANN LA ROCHE
公开号：WO2021234004A1
公开（公告）日：2021-11-25
The present invention relates to compounds which are suitable to be used in mass spectrometry as well as methods of mass spectrometric determination of analyte molecules using said compounds.
本发明涉及适用于质谱的化合物，以及利用该化合物进行分析物分子的质谱测定方法。
[EN] QUINAZOLINE DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] DÉRIVÉS DE QUINAZOLINE, COMPOSITIONS ET UTILISATIONS ASSOCIÉES
申请人：UNIV EMORY
公开号：WO2013181135A1
公开（公告）日：2013-12-05
The disclosure relates to quinazoline derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidases (Nox enzymes) and/or myeloperoxidase.
A pharmaceutically active inventive compound comprises two independently active analgesic moieties covalently conjoined through a physiologically labile linker. A preferred embodiment comprises an opioid, such as morphine, covalently linked to at least one analgesic compound selected from the group consisting of an opioid or a non-opioid compound through a physiologically labile linker. Suitable covalent linkers are covalently bonded to the two independently active analgesic compounds through one or more lactone, lactam, or sulfonamido linkages. Suitable linkers include endogenous carboxylate, amido, and sulfonamido moieties, and exogenous moieties that form the aforementioned lactone, lactam or sulfonamido linkages.
Controlled-release compositions containing opioid agonist and antagonist
申请人：——
公开号：US20020010127A1
公开（公告）日：2002-01-24
Controlled-release dosage forms containing an opioid agonist; an opioid antagonist; and a controlled release material release during a dosing interval an analgesic or sub-analgesic amount of the opioid agonist along with an amount of said opioid antagonist effective to attenuate a side effect of said opioid agonist. The dosage form provides analgesia for at least about 8 hours when administered to human patients. In other embodiments, the dose of antagonist released during the dosing interval enhances the analgesic potency of the opioid agonist.
of sulfation with pyridine-SO(3) complex and sulfuric acid/N,N'-dicyclohexylcarbodiimide. Complete (1)H- and (13)C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circulardichroism and opticalrotatorydispersion revealed characteristic differences in the spectra due
