Steady state pharmacokinetics of propranolol in Saudi Arabian patients and comparison with data for different populations

The steady state pharmacokinetics of propranolol was examined in 48 Saudi Arabian patients chronically treated with oral doses [mean (SEM) = 85.8 (5) mg] of this drug. The mean (SEM) of the steady state concentration (Css) per mg/kg daily dose was 21.8 (3.1) ng.ml-1/mg.kg-1. A 6-fold variability in Css was observed between patients treated with 40 mg every 8 hours and 14-fold between patients treated with 40 mg twice daily. The frequency distribution of the apparent oral clearance (TCLor) of propranolol was bimodal with 88% of the patients showing TCLor of 18 to 372 l.hr-1 while the remainder had TCLor of 471 to 749 l.hr-1. The mean (SEM) of the TCLor per kg body weight for all 48 patients was 3.16 (0.38) l.hr-1.kg-1. Both Css and TCLor obtained for Saudi Arabian patients are not significantly different from those reported for subjects from Western populations. While Css increased proportionally (P less than .001) with dosing, a near-significant (P less than .06), inverse, linear relationship was found between age and TCLor. No significant effect of sex, body weight, or disease state (i.e., heart diseases, hypertension, depression, migraine) on Css or TCLor was detected.