levosalbutamol:药物动力学的临床意义是什么?
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博尔顿DW,福塞特JP
levosalbutamol:药物动力学的临床意义是什么?
Pharmacokinet。2001年1月,40 (1):23-40。
- PubMed ID
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11236808 (在PubMed]
- 文摘
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舒喘灵(沙丁胺醇)是一个beta2-adrenoceptor受体激动剂作为支气管扩张剂治疗哮喘和作为暂停的子宫弛缓的早产。舒喘灵已经销售外消旋混合物,尽管beta2-agonist活动几乎完全驻留在(R)对映体。舒喘灵的拆分性格和(S)舒喘灵有不利影响的可能性导致光学纯的开发(R)舒喘灵配方称为levosalbutamol (levalbuterol)。舒喘灵是生物几乎完全sulphotransferase(饥饿)1 a3活性代谢物。(R)舒喘灵是生物新陈代谢12倍舒喘灵(年代)。这导致等离子体浓度较高(S) -舒喘灵之后的所有航线管理,尤其是口服后由于小肠广泛的代谢。对映体浓度相似吸入剂量后的第一个小时,反映这一事实舒喘灵肺部可能发生小的新陈代谢。随后,(S)舒喘灵主导由于吸收和代谢的吞下部分吸入剂量。光学纯口服或吸入管理舒喘灵后,少量(6%)被转换为其他对映体,可能由acid-catalysed racemisation的腹部。组织结合舒喘灵不是拆分和血浆蛋白结合相对较低。 Both enantiomers are actively excreted into the urine. Compared with healthy individuals, patients with asthma do not have substantially different pharmacokinetics of the salbutamol enantiomers, but they do appear to have less drug delivered to the lung following inhaled administration because of their narrowed airways. Levosalbutamol elicits an equal or slightly larger response than an equivalent dose of the racemic mixture. This is probably due to competitive inhibition between the enantiomers at beta-adrenoceptors. Pharmacokinetic-pharmacodynamic relationships for levosalbutamol show relatively large interindividual variations. Functionally significant genetic polymorphisms have been identified for beta2-adrenoceptors, SULT1A3 and organic action transporters, all of which affect the disposition or action of levosalbutamol. Animal, in vitro and some clinical studies have reported deleterious effects of (S)-salbutamol on smooth muscle contractility or lung function. However, well-designed clinical studies in patients with asthma have failed to find evidence of significant toxicity associated with (S)-salbutamol. The clinical consequences of relatively higher plasma concentrations of (S)-salbutamol following administration of racemate remain unclear, but in the absence of clear evidence of toxicity the clinical superiority of levosalbutamol over racemic salbutamol appears to be small.
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- 药物