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药品详细

Buprenorphine(丁丙诺啡)

化学结构式图
中文名
丁丙诺啡
英文名
Buprenorphine
分子式
C29H41NO4
化学名
(1S,2R,6S,14R,15R,16R)-3-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-3-azahexacyclo[13.2.2.1^{2,8}.0^{1,6}.0^{6,14}.0^{7,12}]icosa-7,9,11-trien-11-ol
分子量
Average: 467.6401
Monoisotopic: 467.303558805
CAS号
52485-79-7
ATC分类
N02A 未知;N07B 未知
药物类型
small molecule
阶段
illicit, approved
商品名
同义名
基本介绍

Buprenorphine is a derivative of the opioid alkaloid thebaine that is a more potent (25 – 40 times) and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [PubChem]

生产厂家
  • Barr laboratories inc
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Pharmaforce inc
  • Purdue pharma lp
  • Reckitt benckiser pharmaceuticals inc
  • Roxane laboratories inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Huang P, Kehner GB, Cowan A, Liu-Chen LY: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist. J Pharmacol Exp Ther. 2001 May;297(2):688-95. Pubmed
  2. Bodkin JA, Zornberg GL, Lukas SE, Cole JO: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. Pubmed
  3. FDA label
  4. Elkader A, Sproule B: Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005;44(7):661-80. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication For the treatment of moderate to severe pain, peri-operative analgesia, and opioid dependence.
Pharmacodynamics Buprenorphine is a synthetic opioid analgesic and thebaine derivative, with a longer duration of action than morphine. Buprenorphine interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, buprenorphine exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Buprenorphine may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Buprenorphine depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Pharmacological effects peaks at 15 minutes and persists for 6 hours or longer when given intramuscularly. When given intravenously, the time to onset and peak effect are shortened.
Mechanism of action Buprenorphine's analgesic effect is due to partial agonist activity at mu-opioid receptors. Buprenorphine is also a kappa-opioid receptor antagonist. The partial agonist activity means that opioid receptor antagonists (e.g., an antidote such as naloxone) only partially reverse the effects of buprenorphine. The binding to the mu and kappa receptors results in hyperpolarization and reduced neuronal excitability. Furthermore, buprenorphine slowly dissociates from its receptor. This observation would account for the longer duration of action compared to morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence. Its receptor fixation half life is 40 minutes which is significantly longer than morphine (milliseconds).
Absorption 31% bioavailability (sublingual). Sublingual absorption is also dependent on pH. The length of time the tablet is under the tongue has little effect on absorption. Although buprenorphine is rapidly absorbed from the oral mucosa, the absorption into the systemic is slower. The time to reach peak plasma concentration (Tmax) varies between individuals (range of 40 minutes to 3.5 hours). How buprenorphine is formulated does not affect this pharmacokinetic parameter. It also undergoes extensive first-pass metabolism and as a consequence, has very low oral bioavailability. Coadministration with naloxone does not effect the pharmacokinetics of buprenorphine.
Volume of distribution

Buprenorphine is very lipophillic and is thus highly distributed. The estimated volume of distribution is 188 – 335 L when given intravenously. It is able to cross into the placenta and breast milk.
Protein binding 96% protein bound to alpha- and beta-globulin.
Metabolism
Hepatic. Buprenorphine undergoes both N-dealkylation to norbuprenorphine and glucuronidation. The N-dealkylation pathway is mediated by cytochrome P-450 3A4 isozyme. Norbuprenorphine, an active metabolite and has one-fifth of the pharmacologic activity of the parent compound, can further undergo glucuronidation.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Buprenorphine
Norbuprenorphine Details
Buprenorphine
Hydroxybuprenorphine Details
Buprenorphine
Buprenorphine glucuronide Details
Route of elimination Buprenorphine, like morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. It is primarily eliminated via feces (as free forms of buprenorphine and norbuprenorphine) while 10 - 30% of the dose is excreted in urine (as conjugated forms of buprenorphine and norbuprenorphine).
Half life IV administration, 0.3 mg = 1.2 - 7.2 hours (mean 2.2 hours); Sublingual administration = 37 hours.
Clearance

Clearance may be higher in children than in adults.
Plasma clearance rate, IV administration, anaesthetized patients = 901.2 ± 39.7 mL/min;
Plasma clearance rate, IV administration, healthy subjects = 1042 – 1280 mL/min.
Toxicity Manifestations of acute overdose include pinpoint pupils, sedation, hypotension, respiratory depression and death.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
logP 4.98 AVDEEF,A ET AL. (1996)
pKa 8.31 (at 25 °C) AVDEEF,A ET AL. (1996)
Predicted Properties
Property Value Source
water solubility 1.68e-02 g/l ALOGPS
logP 4.53 ALOGPS
logP 3.55 ChemAxon
logS -4.4 ALOGPS
pKa (strongest acidic) 7.5 ChemAxon
pKa (strongest basic) 12.54 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 62.16 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 131.76 ChemAxon
polarizability 53.11 ChemAxon
药物相互作用
Drug Interaction
Alvimopan Opioids like buprenorphine may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Consider therapy modification.
Atazanavir Atazanavir may increase the serum concentration of Buprenorphine. Buprenorphine may decrease the serum concentration of Atazanavir. Avoid use of buprenorphine in patients receiving atazanavir without ritonavir boosting due to possible decreases in atazanavir exposure. In patients receiving buprenorphine with atazanavir/ritonavir, monitor for increased buprenorphine effects and consider dose reductions if patients experience adverse effects.
Conivaptan Conivaptan may increase the serum concentration of CYP3A4 Substrates like buprenorphine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
Droperidol Droperidol may enhance the CNS depressant effect of CNS Depressants like buprenorphine. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.
Etravirine Buprenorphine, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to monitor for a decrease in buprenorphine levels (ie. reduced analgesia, and signs of opioid withdrawal).
Isocarboxazid Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like isocarboxazid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Linezolid Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like linezolid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Moclobemide Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like moclobemide. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Phenelzine Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like phenelzine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Procarbazine Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like procarbazine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Rasagiline Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like rasagiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Selegiline Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like selegiline. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Telithromycin Telithromycin may reduce clearance of Buprenorphine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Buprenorphine if Telithromycin is initiated, discontinued or dose changed.
Tranylcypromine Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like tranylcypromine. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
Triprolidine The CNS depressants, Triprolidine and Buprenorphine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of buprenorphine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of buprenorphine if voriconazole is initiated, discontinued or dose changed.
食物相互作用
Not Available

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