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Comparative Pharmacokinetics of Intravenous Propranolol in Obese and Normal Volunteers
Author(s) -
Cheymol Georges,
Poirier JeanMarie,
Barre Jérôme,
Pradalier André,
Dry Jean
Publication year - 1987
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1987.tb05582.x
Subject(s) - pharmacokinetics , propranolol , volume of distribution , medicine , endocrinology , body weight , chemistry
Plasma pharmacokinetics of a single IV dl‐propranolol dose (8 mg) were investigated in 12 obese subjects (mean ± SD: 110.3 ± 20.4 kg; 198.7 ± 32.5% of ideal body weight) and compared with those of 12 healthy subjects (66.7 ± 6.8 kg; 94.5 ± 7.8% of ideal body weight). In obese subjects plasma alpha‐1 glycoprotein acid concentrations and propranolol protein binding capacity did not differ significantly from control subjects. When compared with controls, obese subjects showed a significant increase ( P < .01) in AUC (161.0 ± 67.0 vs 109.6 ± 23.1 hr · μg/L), and significant decreases ( P < .01) in V ss (208.9 ± 71.9 vs 318.6 ± 91.8 L), Vβ (234.3 ± 70.4 vs 340.7 ± 89.1 L), and total clearance (57.5 ± 18.3 vs 75.9 ± 15.4 L/hr). Elimination half‐life was similar for the two populations (3.5 ± 0.9 hr in obese subjects vs 3.1 ± 0.9 hr in controls). Therefore, neither lipophilicity of propranolol nor drug plasma protein binding can explain these data. Altered hepatic function and tissue blood flow in obese subjects are proposed as an explanation for the decrease in total clearance and volume of distribution.