Effects of age and smoking on the pharmacokinetics of pindolol and propranolol.

Abstract

1 Pharmacokinetic investigations were carried out in a group of 32 ambulant normal male volunteers in order to determine the effect of age and smoking on steady‐state plasma levels of pindolol and propranolol. There were four groups of 8: young non‐smokers (YNS), young smokers (YS), old non‐smokers (ONS) and old smokers (OS). Each subject received, in a randomized cross‐over sequence, 5 mg pindolol and 80 mg propranolol three times daily for 2 days with an interval of at least 14 days between the two treatment periods. 2 Neither age nor smoking was shown to have any influence on the time to reach a peak plasma level after pindolol or propranolol. Age, on the other hand, significantly increased the peak plasma levels and the areas under the plasma concentration time curves, and decreased the elimination rate constants, the differences between the age groups being more pronounced for propranolol than for pindolol. No effect of smoking on these parameters was observed. 3 Differences were found between pindolol and propranolol in respect of time to reach a peak plasma level, peak plasma levels and area under the plasma concentration time curves in the groups ONS and YS when related to the YNS control group. Changes observed (with the exception of the time to reach a peak level) tended to be less for pindolol and were considered to be of little clinical relevance.

Enantioselectivity in the steady‐state pharmacokinetics and transplacental distribution of pindolol at delivery in pregnancy‐induced hypertension

“…The clearances of sotalol, digoxin, terbutaline, clorazepate, dexamethasone, methimazole, carbamazepine, phenobarbitone, phenytoin, primidone, pancuronium, ampicillin, cefazolin, cefuroxime, cephradine, and morphine are all increased during pregnancy. 13,21-23 The elimination half-life of pindolol administered in the form of the racemic mixture to healthy volunteers ranges from 3-4 h. 17,[24][25][26] In the present study, the elimination half-lives of the pindolol isomers were slightly lower, with an approximate value of 2.9 h being obtained for both enantiomers. The elimination half-life of pindolol does not differ between pregnant and nonpregnant patients, probably since the increase in the apparent clearance of both enantiomers during pregnancy is compensated for by an increase in the apparent volume of distribution.…”

Antihypertensive Therapy in the Aged Patient

“…Like labetalol (see section 2.2.5), pindolol has been shown to decrease total peripheral resistance and will not further compromise heart rate in the patient with a low resting heart rate (Toth et a,l. The Cmax and AVC of pindolol are significantly increased in elderly patients (Hitzenberger et al: 1982) and the tl/2 is increased 50 to 90% (Frishman 1983;Gretzer et al 1986). However, 2 studies in the elderly (Allegraud 1978;Persson 1978) indicated that 57 to 61% of elderly patients needed concomitant therapy with diuretics to attain adequate antihypertensive control.…”

Comparison of pharmacokinetic profiles of single and multiple doses of a slow release Oros oxprenolol delivery system in young normotensive and elderly hypertensive subjects.

“…Similar observations of increased plasma o' +1 +1 concentrations of 1-adrenoceptor blockers in elderly patients as compared to younger subjects have been made for propranolol (Castleden o . X & George, 1979;Hitzenberger et al, 1982), . pindolol (Hitzenberger et al, 1982) atenolol +1 +1 (Rigby et al, 1985) and acebutolol (Roux et al, 1983).…”

“…X & George, 1979;Hitzenberger et al, 1982), . pindolol (Hitzenberger et al, 1982) atenolol +1 +1 (Rigby et al, 1985) and acebutolol (Roux et al, 1983). However, other comparisons of the kinetics in young and old healthy subjects have a failed to reveal differences for propranolol (Schneider et al, 1980;Rigby et al, 1985), or°m etoprolol (Quarterman et al, 1981;Rigby et X .o * 2 al., 1985).…”