Cheymol G
Service de Pharmacologie, hôpital St-Antoine, Paris.
Bull Acad Natl Med. 1990 Oct;174(7):959-67; discussion 967-8.
We compared in obese patients and normal subjects, the pharmacokinetics of three drugs with different solubility: d,l-sotalol markedly hydrophilic, d,l-propranolol highly lipophilic, d,l-bisoprolol moderately lipophilic. In obese subjects the pharmacokinetic data calculated for sotalol (total clearance (CL), volume of distribution (V beta), half-life of elimination (t1/2), were comparable with those measured in the controls. Data on bisoprolol showed that total V beta increased with excess of body weight, but V beta/kg of body weight was lower in obese subjects than in the controls, CL tended to increase and t1/2 was similar. As concerned propranolol, total V beta and V beta/kg were significantly lower in obese than in control subjects. Cl was decreased in obese patients and t1/2 was similar for both groups. It appears that in the obese the diffusion of liposoluble beta-blockers in the fatty excess weight remains limited. It is possible that a vasoconstrictive effect induced by beta-blockers in adipose tissues could restrict their tissular distribution.
d,l-索他洛尔具有明显的亲水性,d,l-普萘洛尔具有高度的脂溶性,d,l-比索洛尔具有中等脂溶性。在肥胖受试者中,索他洛尔的药代动力学数据(总清除率(CL)、分布容积(Vβ)、消除半衰期(t1/2))与对照组中测得的数据相当。比索洛尔的数据显示,总Vβ随体重增加而增加,但肥胖受试者每千克体重的Vβ低于对照组,CL有增加趋势且t1/2相似。至于普萘洛尔,肥胖者的总Vβ和每千克体重的Vβ显著低于对照组。肥胖患者的CL降低,两组的t1/2相似。看来在肥胖者中脂溶性β受体阻滞剂在多余脂肪中的扩散仍然有限。β受体阻滞剂在脂肪组织中诱导的血管收缩作用可能会限制其组织分布。