Bambuterol (INN) is a long-acting β adrenoceptor agonist (LABA) used in the treatment of asthma; it also is a prodrug of terbutaline. Commercially, the AstraZeneca pharmaceutical company produces and markets bambuterol as Bambec and Oxeol.[1]
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 Bambuterol (top), and (R)-bambuterol (bottom) | |
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| Routes of administration | Oral (tablets) |
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| Pharmacokinetic data | |
| Bioavailability | 20% |
| Metabolism | Extensive hepatic. Further metabolized to terbutaline by plasma cholinesterase |
| Elimination half-life | 13 hours (bambuterol) 21 hours (terbutaline) |
| Excretion | Renal |
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| Formula | C18H29N3O5 |
| Molar mass | 367.446 g·mol−1 |
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| Chirality | Racemic mixture |
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It is not available in the U.S.
Indications
editAs other LABAs, bambuterol is used in the long-term management of persistent asthma.[1] It should not be used as a rescue medication for short-term relief of asthma symptoms.
Contraindications
editBambuterol is contraindicated in pregnancy and in people with seriously impaired liver function. It can be used by people with renal impairment, but dose adjustments are necessary.[1]
Adverse effects
editThe adverse effect profile of bambuterol is similar to that of salbutamol, and may include fatigue, nausea, palpitations, headache, dizziness and tremor.[1]
Interactions
editConcomitant administration of bambuterol with corticosteroids, diuretics, and xanthine derivatives (such as theophylline) increases the risk of hypokalemia (decreased levels of potassium in the blood).[2]
Bambuterol acts as a cholinesterase inhibitor, and can prolong the duration of action of suxamethonium (succinylcholine) and other drugs whose breakdown in the body depends on cholinesterase function.[1] Butyrylcholinesterase activity returns to normal approximately two weeks after bambuterol is stopped.[3] It can also enhance the effects of non-depolarizing neuromuscular blockers, such as vecuronium bromide.[2]
Synthesis
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The reaction between 3',5'-Dihydroxyacetophenone [51863-60-6] (1) and Dimethylcarbamoyl chloride [79-44-7] (2) gives 5-Acetyl-1,3-phenylene bis(dimethylcarbamate) [81732-48-1] (3). Halogenation with bromine led to 5-(Bromoacetyl)-1,3-phenylene bis(dimethylcarbamate) [81732-49-2] (4). Treatment with N-(tert-Butyl)benzylamine [3378-72-1] (5) afforded [81732-47-0] (6). Catalytic hydrogenation completed the synthesis of bambuterol (7).
References
edit- ^ a b c d e Sweetman SC, ed. (2009). "Bronchodilators and Anti-asthma Drugs". Martindale: The complete drug reference (36th ed.). London: Pharmaceutical Press. pp. 1115–16. ISBN 978-0-85369-840-1.
- ^ a b Sweetman (2009), pp. 1132–33.
- ^ Sitar DS (October 1996). "Clinical pharmacokinetics of bambuterol". Clinical Pharmacokinetics. 31 (4): 246–56. doi:10.2165/00003088-199631040-00002. PMID 8896942. S2CID 25696134.
- ^ Castaer, J.; Prous, J.; Bambuterol. Drugs Fut 1986, 11, 7, 553.
- ^ EP0043807 idem Otto Agne Olsson, et al. U.S. patent 4,419,364 (1983 to DRACO AB); CA, 96, 199263.
- ^ 김신종, et al. KR100803291 (2008).
- ^ 唐冬军 & 寇景平, CN104262202 (2016 to Guangdong HEC Pharmaceutical).
- ^ Asami, K., Machida, T., Jung, S., Hanaya, K., Shoji, M., Sugai, T. (December 2013). "Synthesis of (R)-bambuterol based on asymmetric reduction of 1-[3,5-bis(dimethylcarbamoyloxy)phenyl]-2-chloroethanone with incubated whole cells of Williopsis californica JCM 3600". Journal of Molecular Catalysis B: Enzymatic. 97: 106–109. doi:10.1016/j.molcatb.2013.08.003.
- ^ Cao, G., Hu, A., Zou, K., Xu, L., Chen, J., Tan, W. (July 2008). "Highly enantioselective synthesis, crystal structure, and circular dichroism spectroscopy of ( R )-bambuterol hydrochloride". Chirality. 20 (7): 856–862. doi:10.1002/chir.20558.