Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults

Department of Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects o...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2002-02, Vol.282 (2), p.H704-H716
Main Authors: Bramswig, Susanne, Kerksiek, Anja, Sudhop, Thomas, Luers, Claus, Von Bergmann, Klaus, Berthold, Heiner K
Format: Article
Language:English
Subjects:
Adult
Anticonvulsants - administration & dosage
Anticonvulsants - adverse effects
Arteriosclerosis - blood
Body Composition
Body Weight
Carbamazepine - administration & dosage
Carbamazepine - adverse effects
Cholestanol - blood
Cholestanol - pharmacokinetics
Cholesterol - analogs & derivatives
Cholesterol - blood
Cholesterol, HDL - biosynthesis
Cholesterol, HDL - blood
Cholesterol, LDL - biosynthesis
Cholesterol, LDL - blood
Cholesterol, VLDL - biosynthesis
Cholesterol, VLDL - blood
Diet
Humans
Hydrocortisone - analogs & derivatives
Hydrocortisone - blood
Intestinal Absorption
Lipoproteins - biosynthesis
Lipoproteins - blood
Male
Mevalonic Acid - blood
Mevalonic Acid - urine
Phytosterols - blood
Phytosterols - pharmacokinetics
Sitosterols - blood
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Summary:Department of Clinical Pharmacology, University of Bonn, 53105 Bonn, Germany Treatment with carbamazepine (CBZ) affects cholesterol concentrations, but little is known about the precise nature and underlying mechanisms of changes in lipoprotein metabolism. We investigated prospectively the effects of CBZ on lipid metabolism in normolipemic adults. In 21 healthy males, lipoprotein and noncholesterol sterol concentrations were measured before and during treatment with CBZ for 70 ± 18 days. Thirteen subjects underwent kinetic studies of apolipoprotein-B (ApoB) metabolism with the use of endogenous stable isotope labeling. Lipoprotein kinetic parameters were calculated by multicompartmental modeling. Significant increases in total cholesterol, in ApoB-containing lipoproteins [very-low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low-density lipoprotein (LDL)], and in triglycerides, but not in high-density lipoprotein (HDL), were observed. Lipoprotein particle composition remained unchanged. Mean fractional catabolic and production rates of ApoB-containing lipoproteins were not significantly different, although mean production rates of VLDL and IDL were substantially increased (+46 ± 139% and +30 ± 97%, respectively), whereas mean production of LDL remained unchanged (+2.1 ± 45.6%). Cholestanol in serum increased significantly but not the concentrations of plant sterols (campesterol, sitosterol) and the cholesterol precursors (lathosterol, mevalonic acid). There was a significant correlation between the decrease in free thyroxine and the increase in IDL cholesterol. Treatment with CBZ increases mainly ApoB-containing lipoproteins. CBZ seems not to influence endogenous cholesterol synthesis or intestinal absorption directly. The increase is neither related to increased ApoB production nor to decreased catabolism but is rather due to changes in the conversion cascade of IDL particles, most likely as an indirect effect through a decrease in thyroid hormones. cholesterol; stable isotopes; apolipoproteins
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00580.2001