Disease relevance of BAMBUTEROL HYDROCHLORIDE

• However, in the first month of exposure the adjusted relative risk of non-fatal ischaemic heart disease was 3.95 (95% CL 1.38 to 11.31) when bambuterol was compared with nedocromil [1].
• In vivo, bambuterol (50-500 microg/kg s.c.) decreased BChE activity peripherally but not in brain tissue and induced apnea and death in adult and neonate AChE-/- mice without affecting littermate AChE+/+ and +/- animals [2].
• Earlier studies in healthy volunteers and in patients with noninsulin dependent diabetes mellitus have shown that terbutaline and bambuterol increase HDL cholesterol levels, and therefore bambuterol might have beneficial effects on HDL levels in patients with hyperlipidaemia [3].
• However, bambuterol, but not salmeterol, caused tremor in several subjects and elicited a more pronounced tachycardia [4].

High impact information on BAMBUTEROL HYDROCHLORIDE

• Pharmacokinetics and pharmacodynamics of bambuterol, a long-acting bronchodilator pro-drug of terbutaline, in young and elderly patients with asthma [5].
• Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol [6].
• Budesonide reduced both eosinophil numbers and ECP levels, especially at night; bambuterol had no effect on both variables [6].
• Both budesonide and bambuterol improved responsiveness more at night than during daytime, thus decreasing circadian variation: at 4 AM, increases in PC20 were 2.0 DC after budesonide and 0.8 DC after bambuterol, compared with placebo [7].
• Rates and relative risks of non-fatal cardiac failure and ischaemic heart disease were calculated, comparing bambuterol and salmeterol with the reference drug nedocromil [1].

Biological context of BAMBUTEROL HYDROCHLORIDE

• The results of the hydrolysis experiments once again illustrate the difference in affinity of bambuterol to the genetic forms of cholinesterase, and also strengthen the evidence that cholinesterase is the major serum enzyme catalysing the hydrolysis of bambuterol [8].
• Interactions of bambuterol with human serum cholinesterase of the genotypes EuEu (normal), EaEa (atypical) and EuEa [8].
• The heterozygotes showed a mixed behaviour; the major activity was inhibited like the normal enzyme (IC50 = 9.3 +/- 1.9 nM, N = 9), while a residual activity (10-15%) was inhibited by bambuterol like the atypical enzyme [8].
• The IC50 for the normal enzyme was 11 +/- 2.2 nM (mean, SD, N = 10) and for the atypical enzyme 140 +/- 6 nM (N = 13), indicating a much higher affinity of bambuterol to the normal enzyme [8].
• The 24-h mean FEV1 was greater (p < 0.001) for bambuterol (morning: 3.2 L; evening: 3.4 L) vs placebo (2.9 L) as it was for FVC, FEF25-75%, and peak expiratory flow rate (PEFR), with the maximum effect at 4 AM independent of medication time [9].

Anatomical context of BAMBUTEROL HYDROCHLORIDE

• Bambuterol is stable to presystemic elimination and is concentrated by lung tissue after absorption from the gastrointestinal tract [10].
• These quantitative data are supplemented by morphological observations in retinal explant cultures grown on striped laminin carpets, viz., defasciculation of neurite bundles by BW 284C51 and Bambuterol occurs, indicating that these drugs disturb adhesive mechanisms [11].
• Metabolism of bambuterol in rat liver microsomes: identification of hydroxylated and demethylated products by liquid chromatography mass spectrometry [12].
• However orally administered terbutaline, as the active drug itself or released from its pro-drug bambuterol, did not inhibit mast cell activation or allergic skin responses [13].
• Thus, the rates of transport of bambuterol and terbutaline from plasma into the central nervous system appear to be slow relative to transport out of the system, e.g. by outflow of CSF [14].

Associations of BAMBUTEROL HYDROCHLORIDE with other chemical compounds

• This paper presents age- and gender-specific asthma death rates in patients prescribed the long-acting beta2-agonists salmeterol and bambuterol [15].
• The lung uptake of bambuterol was significantly (0.05 greater than or equal to P greater than or equal to 0.001) higher than that found for sucrose in single-pass perfusion experiments [16].
• The influence of 10 mg and 20 mg of bambuterol on the duration of succinylcholine-induced neuromuscular blockade [17].
• Suitable HPLC methods for the direct separation of bambuterol and albuterol enantiomers were developed [18].

Gene context of BAMBUTEROL HYDROCHLORIDE

• The present study aimed at investigating the fate of bambuterol in subjects with deficient plasma cholinesterase but with normal oxidative (CYP2D6) capability [19].
• The objective of this research was, consequently, to compare the efficacy and safety of 20 mg oral bambuterol and 50 microg inhaled salmeterol in patients with partially reversible COPD [4].
• The bimolecular rate constant of AChE w.t. inhibition was 6.8 times smaller by Ro 02-0683 and 16000 times smaller by bambuterol than that of BChE w.t. The two carbamates were equipotent BChE inhibitors [20].
• Plasma butyrylcholinesterase activity returns to control values approximately 2 weeks after discontinuation of treatment with bambuterol [10].
• Except for the suppression of plasma butyrylcholinesterase, the adverse effect profile of bambuterol is essentially that of a beta 2 agonist and is best correlated with circulating terbutaline concentration in plasma [10].

Analytical, diagnostic and therapeutic context of BAMBUTEROL HYDROCHLORIDE

• A hollow fiber miniaturized supported liquid membrane (SLM) device for sample preparation is connected on-line with capillary electrophoresis and used for determination of a basic drug, bambuterol, in human plasma [21].
• DESIGN: The present study was a randomized, double-blind, crossover study, comparing 20 mg of bambuterol with placebo, each one given for 6-8 weeks with a 3-4 week washout period in between [3].
• Pharmacokinetics of bambuterol during oral administration of plain tablets and solution to healthy adults [22].
• High-performance liquid chromatographic (HPLC) analysis showed that 95.6 +/- 3.6% of the effluent 3H radioactivity was attributable to bambuterol [16].
• One-year safety study with bambuterol once daily and terbutaline three times daily in 2-12-year-old children with asthma. The Bambuterol Multicentre Study Group [23].

References