Effects of gemfibrozil on the oxygen transport properties of erythrocytes.
1. In the present study we have investigated the effects of the relatively low plasma concentrations of gemfibrozil (GFZ) found in clinical practice on the oxygen dissociation curve (ODC) of erythrocytes. 2. ODCs were measured at 30 degrees C and 37 degrees C and at pH 7.4: a) both on HbA solution and erythrocytes incubated in vitro with gemfibrozil and clofibric acid; b) on erythrocytes from healthy volunteers treated with a single oral dose of gemfibrozil. 3. These experiments showed a significant drug-induced shift of the ODC towards lower O2 affinity values without any significant modification of metabolic parameters of erythrocytes such as intracellular pH and intraerythrocytic levels of ATP and DPG. 4. In our experimental conditions gemfibrozil appears to lower both in vitro and in vivo, the partial pressure of oxygen required to give 50% of the haemes saturated with oxygen (P50) of erythrocytes from the control value of 24 +/- 0.5 mm Hg to 29 +/- 0.5 mm Hg (mean +/- s.d.; P < 0.02 by ANOVA). 5. These data clearly indicate that therapeutic doses of gemfibrozil may influence the oxygen transport properties of red cells. This effect could have relevant pharmacological and toxicological implications.
Scatena
R
R
Institute of Chemistry and Clinical Chemistry, Faculty of Medicine, Catholic University, Rome, Italy.
Nocca
G
G
Messana
I
I
De Sole
P
P
Baroni
S
S
Zuppi
C
C
Castagnola
M
M
Giardina
B
B
D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate / Q000097:blood; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects; D004163:Diphosphoglyceric Acids / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D015248:Gemfibrozil / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008875:Middle Aged; D010100:Oxygen / Q000097:blood*
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D019794:2,3-Diphosphoglycerate; D000255:Adenosine Triphosphate; D015248:Gemfibrozil; D010100:Oxygen