Influence of physical exercise on the pharmacokinetics of propranolol

Abstract

The pharmacokinetics of propranolol after oral and intravenous administration was studied at rest and on an exercise day in 8 healthy subjects. On the exercise day the subjects performed physical exercise for 7 h, consisting of bicycle ergometer exercise at 50% of maximal work capacity and outdoor walking. Propranolol (80 mg p.o., or 0.2 mg/kg body weight i.v.) was administered 30 min before the start of the exercise. After oral administration the terminal phase halflife, (t1/2 beta) and area under the curve (AUC) were both significantly reduced on the exercise day compared to the rest day. The bioavailability of propranolol was reduced by prolonged physical exercise and plasma levels of propranolol were about 30% lower at the end of the exercise day than at the end of the rest day. After intravenous administration, t1/2 beta was also reduced on the exercise day as compared to the rest day. AUC, clearance and volume of distribution did not differ on the two days. On the other hand, indocyanine green (ICG) clearance was significantly reduced during the bicycle ergometry periods on the exercise day. The combination of reduced ICG clearance, suggesting a reduction in hepatic blood flow, and a decreased t1/2 beta and unchanged clearance of propranolol on the exercise day was unexpected.

Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach

“…On the other hand, midazolam absorption decreases during moderate exercise, as evidenced by decreased maximal drug concentration (C max ) and absorption rate constant (k a ) and an increased T max in comparison with that at rest (Strömberg et al 1992). In the case of propranolol, bioavailability is reduced during exercise (Arends et al 1986). In most cases, however, no change in absorption has been observed during exercise for quinidine, sodium salicylate, and sulphadimidine (Aslaksen and Aanderud 1980) as well as ephedrine (Strömberg et al 1992) compared with that at rest.…”

Effect of exercise on disposition and pharmacokinetics of drugs

“…A number of studies have shown that clearance is a function of hepatic blood flow for many flow-limited drugs, including bromosulfophthalein [Brauer, 19631, hydrocortisone [Paterson and Harrison, 19721, oxyphenbutazone [Whitsett et al, 19711, and lidocaine [Thornson et al, 19711. Experiments studying the effect of exercise on drug elimination of flow-limited drugs have generally agreed with the blood flow dependency hypothesis. As Table 6 illustrates, clearance was decreased during exercise for some flow-limited drugs, such as ampicillin [Cadorniga et al, 19741, caffeine [Kamimori et al, 1986;Hetzler, 1988;Hetzler et al, 19901, ICG [Swartz et al, 1974;Daneshmend et al, 1981;Arends et al, 1986;Mooy et al, 19861, pralidoxime [Swartz and Sidell, 19731, riboflavin [Belko, 19871, sulphadimidine, acetylsulphadimidine, procainainide [Ylitalo and Hinkka, 19851, testosterone [Cadoux-Hudson et al, 19851, and theophylline [Schlaeffer et al, 19841, although the clearance of antipyrine was not significantly changed [Swartz et al, 1974;Theilade et al, 19791. Propranolol, which is flow-limited [Branch et al, 19731, should probably also have a decreased clearance. A study by Arends et al [ 19851 showed a decreased half-life after oral administration of propranolol.…”

Effects of a finnish sauna on the pharmacokinetics and haemodynamic actions of propranolol and captopril in healthy volunteers

“…The elimination half-life of propranolol, on the other hand, remained unchanged which means that the volume of distribution / clearanceratio of the drug was also unchanged. As has been shown during physical exercise, by decreased indocyanine green clearance (Arens et al 1986), a reduction in hepatic blood flow does not necessarily reduce the clearance of propranolol. On the basis of the theoretical reduction in hepatic blood flow both during exercise and a sauna, certain discrepancies were also observed in our previous studies, when the sauna led to a reduction in the AUC04~ of midazolam, another drug extensively metabolised during first-pass circulation, whereas exercise did not affect the midazolam AUC (Str6mberg et al 1992;Vanakoski et al 1993).…”