[Effect of hydroxylation polymorphism on the concentration of propranolol in the blood of humans with hyperlipidemia].
An influence of hydroxylation phenotype on the concentration of propranolol [corrected] was examined in 52 subjects with hyperlipidemia divided into 4 groups: 1--control, normolipemic, 2--hypercholesterolemic, 3--hypertriglyceridemic, and 4--mixed-form hyperlipidemic. Each study group included extensive metabolizers and one subject characterized by a poor hydroxylation phenotype. Propranolol was given intragastrically at a single dose of 80 mg [corrected]. Blood was sampled within 24 hours following the drug administration. HPLC method was used for determining blood serum concentrations of propranolol. In each study group mean blood serum concentrations of propranolol in poor metabolizers were at maximum in subject with hypertriglyceridemia, at minimum in the normolipemic one, and intermediate in hypercholesterolemic (upper) and mixed-form hyperlipidemic ones. Lipid metabolic disturbances also affected blood serum concentrations. They were the highest in hypertriglyceridemic patients, whereas in hypercholesterolemic were, in early stage of observation, even lower then in normolipemic subjects. Blood serum concentrations of propranolol [corrected] attained minimal values in patients with mixed form of hyperlipidemia. In the light of the present study we can state that hyperlipidemia modifies the blood serum concentrations of propranolol [corrected]. Although, the type of hyperlipidemia and lipophilic propranolol are not the only determinants affecting blood serum concentrations of propranolol, but also a genetic factor, i.e. hydroxylation phenotype may play an important role.
Sulzyc-Bielicka
V
V
Zakładu Farmakologii Doświadczalnej i Klinicznej PAM w Szczecinie.
Droździk
M
M
Gawrońska-Szklarz
B
B
Sterna
R
R
Wójcicki
J
J
Kunicki
P
P
Sitkiewicz
D
D
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D006949:Hyperlipidemias / Q000097:blood* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010641:Phenotype; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics*
D000959:Antihypertensive Agents; D011433:Propranolol; D006899:Mixed Function Oxygenases