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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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| Published in: | American journal of physiology. Heart and circulatory physiology 2002-02, Vol.282 (2), p.H704-H716 |
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| container_end_page | H716 |
| container_issue | 2 |
| container_start_page | H704 |
| container_title | American journal of physiology. Heart and circulatory physiology |
| container_volume | 282 |
| creator | Bramswig, Susanne Kerksiek, Anja Sudhop, Thomas Luers, Claus Von Bergmann, Klaus Berthold, Heiner K |
| description | 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 |
| doi_str_mv | 10.1152/ajpheart.00580.2001 |
| format | article |
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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.
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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</description><subject>Adult</subject><subject>Anticonvulsants - administration & dosage</subject><subject>Anticonvulsants - adverse effects</subject><subject>Arteriosclerosis - blood</subject><subject>Body Composition</subject><subject>Body Weight</subject><subject>Carbamazepine - administration & dosage</subject><subject>Carbamazepine - adverse effects</subject><subject>Cholestanol - blood</subject><subject>Cholestanol - pharmacokinetics</subject><subject>Cholesterol - analogs & derivatives</subject><subject>Cholesterol - blood</subject><subject>Cholesterol, HDL - biosynthesis</subject><subject>Cholesterol, HDL - blood</subject><subject>Cholesterol, LDL - biosynthesis</subject><subject>Cholesterol, LDL - blood</subject><subject>Cholesterol, VLDL - biosynthesis</subject><subject>Cholesterol, VLDL - blood</subject><subject>Diet</subject><subject>Humans</subject><subject>Hydrocortisone - analogs & derivatives</subject><subject>Hydrocortisone - blood</subject><subject>Intestinal Absorption</subject><subject>Lipoproteins - biosynthesis</subject><subject>Lipoproteins - blood</subject><subject>Male</subject><subject>Mevalonic Acid - blood</subject><subject>Mevalonic Acid - urine</subject><subject>Phytosterols - blood</subject><subject>Phytosterols - pharmacokinetics</subject><subject>Sitosterols - blood</subject><issn>0363-6135</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNp1kNtKw0AQhhdRbK0-gSB5gdQ9ZbPpnRRrBcGber1MkkmzJSd2U7Q-vamt7ZVXMzD_9zN8hNwzOmUs4o-w6UoE108pjTSdckrZBRkPFx6ySCSXZEyFEqFiIhqRG-83dAjGSlyTEWOx1pKzMVnNwaVQwzd2tsHANplD8OgD6Et07RobmwWV7drOtT3axs-CGrMSGuvroC0CyHrbNgMX1FBhAPm26v0tuSqg8nh3nBPysXhezZfh2_vL6_zpLcxkFPehglRqmcWJlCrKc60xSfmwiLjIi1QwqZjWnOcggKYQIS2SLFYypZAoGikqJkQcejPXeu-wMJ2zNbidYdTsHZk_R-bXkdk7GqiHA9Vt0xrzM3OUMgRmh0Bp1-WndWi6cudtW7XrnVlsq2qFX_2pmmtuuFnGVJouLwZ4-j98eucMiR9BmIvG</recordid><startdate>20020201</startdate><enddate>20020201</enddate><creator>Bramswig, Susanne</creator><creator>Kerksiek, Anja</creator><creator>Sudhop, Thomas</creator><creator>Luers, Claus</creator><creator>Von Bergmann, Klaus</creator><creator>Berthold, Heiner K</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20020201</creationdate><title>Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults</title><author>Bramswig, Susanne ; Kerksiek, Anja ; Sudhop, Thomas ; Luers, Claus ; Von Bergmann, Klaus ; Berthold, Heiner K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-6ab484c794465dd88e9b25dd37fdfb314618822da3a0ba5e0f9c764b0a9605603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Adult</topic><topic>Anticonvulsants - administration & dosage</topic><topic>Anticonvulsants - adverse effects</topic><topic>Arteriosclerosis - blood</topic><topic>Body Composition</topic><topic>Body Weight</topic><topic>Carbamazepine - administration & dosage</topic><topic>Carbamazepine - adverse effects</topic><topic>Cholestanol - blood</topic><topic>Cholestanol - pharmacokinetics</topic><topic>Cholesterol - analogs & derivatives</topic><topic>Cholesterol - blood</topic><topic>Cholesterol, HDL - biosynthesis</topic><topic>Cholesterol, HDL - blood</topic><topic>Cholesterol, LDL - biosynthesis</topic><topic>Cholesterol, LDL - blood</topic><topic>Cholesterol, VLDL - biosynthesis</topic><topic>Cholesterol, VLDL - blood</topic><topic>Diet</topic><topic>Humans</topic><topic>Hydrocortisone - analogs & derivatives</topic><topic>Hydrocortisone - blood</topic><topic>Intestinal Absorption</topic><topic>Lipoproteins - biosynthesis</topic><topic>Lipoproteins - blood</topic><topic>Male</topic><topic>Mevalonic Acid - blood</topic><topic>Mevalonic Acid - urine</topic><topic>Phytosterols - blood</topic><topic>Phytosterols - pharmacokinetics</topic><topic>Sitosterols - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bramswig, Susanne</creatorcontrib><creatorcontrib>Kerksiek, Anja</creatorcontrib><creatorcontrib>Sudhop, Thomas</creatorcontrib><creatorcontrib>Luers, Claus</creatorcontrib><creatorcontrib>Von Bergmann, Klaus</creatorcontrib><creatorcontrib>Berthold, Heiner K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bramswig, Susanne</au><au>Kerksiek, Anja</au><au>Sudhop, Thomas</au><au>Luers, Claus</au><au>Von Bergmann, Klaus</au><au>Berthold, Heiner K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2002-02-01</date><risdate>2002</risdate><volume>282</volume><issue>2</issue><spage>H704</spage><epage>H716</epage><pages>H704-H716</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><abstract>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</abstract><cop>United States</cop><pmid>11788421</pmid><doi>10.1152/ajpheart.00580.2001</doi></addata></record> |
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| identifier | ISSN: 0363-6135 |
| ispartof | American journal of physiology. Heart and circulatory physiology, 2002-02, Vol.282 (2), p.H704-H716 |
| issn | 0363-6135 1522-1539 |
| language | eng |
| recordid | cdi_crossref_primary_10_1152_ajpheart_00580_2001 |
| source | American Physiological Society Free |
| 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 |
| title | Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults |
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