Obesity and Beta‐Blockers: Influence of Body Fat on Their Kinetics and Cardiovascular Effects

Abstract

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.

Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

“…The results of pharmacokinetic studies for the healthy controls were similar to those reported by other investigators [11][12][13]. In obese subjects both with and without hyperlipidaemia the pharmacokinetics of propranolol and atenolol were altered, most significantly during the elimination phases.…”

“…Nevertheless, the results of Galletti et al [11] suggested that obesity did not influence the pharmacokinetics of water-soluble b-blockers.…”

“…The variability in lipophilicity could further influence their pharmacokinetics and consequent haemodynamic effects of those drugs in obese patients [9,10]. In the relatively few studies on the kinetics ofblockers in obese patients the authors did not investigate concomitant lipid disorders [11][12][13]. Our previous data suggested that lipid status could influence both the pharmacokinetics and pharmacodynamics of propranolol in hyperlipidaemia [7,14].…”

Measurement of Glomerular Filtration Rate in Obese Patients: Pitfalls and Potential Consequences on Drug Therapy

“…Unfortunately, the pharmacokinetics of antihypertensive drugs have not been studied systematically in obese patients. Obesity has been shown to influence the pharmacokinetics of the lipophilic compound metoprolol without affecting the water-soluble compound atenolol [48]. However the antihypertensive effect seemed not to be influenced.…”

Behandlung der Hypertonie bei Adipositas

“…Obwohl bisher nur wenige diesbezügliche Studien vorliegen, wurden diese Überlegungen bestätigt in einer Studie mit Verapamil, in der bei Adipösen im Vergleich zu Normgewichtigen ein deutlich höheres Distributionsvolumen und eine verlängerte Eliminationshalbwertszeit gemessen wurden [2]. Das gleiche Phänomen wurde unter dem lipophilen Betarezeptorenblocker Metoprolol beschrieben, während der hydrophile Betablocker Atenolol in den pharmakokinetischen Eckdaten unbeeinflusst blieb [21]. Während jedoch in der ersten Studie intravenös verabreichtes Verapamil in seiner Wirkung, d.h. seiner Pharmakodynamik, durch den Fettanteil beeinflusst wurde, war dies bei Metoprolol nicht zu beobachten; sowohl Metoprolol als auch Atenolol wirkten bei norm-und über-gewichtigen Hypertonikern insgesamt weitgehend identisch blutdrucksenkend.…”