â/ '/c/›ii‹i, 40(4):480—484, I '999

I.ippincutl Will iaius & W iik ins, I nc.,

Philadelphia O 1 niernaiional League Against
Epilepsy

Clinical Research

Increased High-Density Lipoprotein Cholesterol in Patients wlth

Epilepsy Treated with Carbamazepine: A Gender-Related Study

T. Sudhop, *J. Bauer, *C. E. Elger, and K. von Bergmann

Departments c›] Clinic’al Phurma‹’olo g5 and *Eyileytolo gv, Unive rsit y oj! Bonn, Bonn, Ge rman v

Summary: Purpose. Long-term treatment with carbamaze-

triglycerides but lower HDL cholesterol in men) was confirmed in
pine (CBZ) may alter serum lipoprotein concentrations. Gen-
controls and patients treated with CBZ, with the exception of LDL
der-related examinations, however, are rare and inconsistent in
cholesterol. The HDL as well as the LDL differences were
their results.
signif’icantly more pronounced in women treated with CBZ
Method,s. To examine possible sex di fterences, serum lipo-
than in men when compared with their controls. These results
proteins were analyzed in 1 27 clinic outpatients (56 women and
were independent of the dose of CBZ and plasma concentra-
7 I men) with epilepsies with focal or secondarily generalized tonic
tions. Lathosterol, a cholesterol precursor, and its ratio to cho-
—clonic seizures (or both) treated with a CBZ mono- therapy.
lesterol, an indicator of cholesterol synthesis, were not differ-
Results were compared with a control group of 177 blood donors
ent, when compared between gender and different HDL groups.
(67 women and 1 10 men) matched for age and weight.
Conclusion,s. The observed increase in HDL cholesterol in
Re.sult.s. Total cholesterol, low-density lipoprotein (LDL)
patients with CBZ, especially in women, might correlate with
cholesterol and high-density lipoprotein (HDL) cholesterol
the previously reported diminished rate of death from coronary
were higher in both male and female patients treated with CBZ
heart disease in patients with epilepsy as HDL exerts an anti-
compared with controls. The known sex difference in serum
athero genie effect. Key Words: Carbamazepine—Lipo-
lipoprotein concentrations (i.e., higher LDL cholesterol and
proteins—HDL cholesterol—Gender.

In previous studies, it was observed that carbamaze-

pine (CBZ) affects serum lipoprotein concentrations ( 1 — sible effects on cholesterol synthesis in a subgroup of
9). In a prospective study, Isojiirvi et al. (4) reported an patients.
increase in serum concentrations of total cholesterol and
high-density lipoprotein (HDL) cholesterol in patients MATERIALS AND METHODS
treated with CBZ during the entire treatment period. A
Patients
CBZ-related increase of HDL cholesterol, which exerts
Total, low-density lipoprotein (LDL), HDL choles-
an antiatherogenic effect, might be relevant for the inci-
terol, and serum triglycerides were measured in 127
dence and mortality from coronary heart disease ( 10,1 1 ).
clinic outpatients with epilepsies with focal or second-
Indeed, coronary heart disease is supposed to be less
arily generalized tonic—clonic seizures or both (56
common in patients with epilepsy ( 12—14). We were in-
women and 71 men) treated with CBZ as monotherapy.
terested in a further analysis of pathophysiologic mecha-
Some patients received additional, not antiepileptic,
nisms of the effect of CBZ on lipid levels. Furthermore,
drugs, none of which is known to affect lipid metabo-
we focused on gender-related effects, because in healthy
lism. The results were compared with those of 177 blood
subjects, HDL cholesterol is higher in women than in
donors (67 women and 1 10 men) matched for age and
men. This difference is believed to be responsible for the
lower incidence of coronary heart disease (CHD) in weight. All blood samples were taken in an upright sit-
ting position in the morning after an overnight fast of
women (10,15—17). Because CBZ is a strong cytochrome
> 10 h. Clinical characteristics of patients and controls
P-450 enzyme inducer (18-21), we examined also pos-
are summarized in Table 1 . The study was conducted in
accordance with the ethical principles of the declaration
Accepted October 13, I VVS. of Helsinki. All participants gave informed consent.
Address correspondence and reprint requests to Prot. Dr. K. von
Bergmann at Department of Clinical Pharmacology, University of Methods
Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. Total cholesterol was determined by the cholesterol-
oxidase (CHOD-PAP) method, and triglycerides were

480
 SEX DIFFERENCES IN HDL WITH CARBAMAZEPINE 481

TABLE 1. Clinical characteri..stirs in ya/ieniA treated with carbamu Lepine und control.s

Women Men
Carbamazepine Control Carbairazepine Control
(n = 56) (n = 67) (n = 71) (n = 110)
Age (yr) 36 + 12 32 * 13 34 * 1 1 37 + 12
Weight (kg) 66 * 9 65 + 1 3 81 + 12 78 * 10
CBZ dose (mg/day) l,10G + 498 1,287 * 555
CBZ dose per kg (mg/kg) 17 + 9 16 + 7
CBZ plasma level (tig/ml) 8.4 * 2.6 8.4 + 2.5
Duration of CBZ treatment (mo) 67 + 53 62 * 55

Values expressed as mean + SD.

CBZ, carbamazepine.

measured by means of an enzymatic routine kit (Boeh-
ringer, Mannheim, Germany). HDL cholesterol was as-
sayed by CHOD-PAP after precipitation of apolipopro-
tern B containing lipoproteins with phosphotungstic acid
and heparin manganate. LDL cholesterol was calculated
with the Friedewald formula (22). CBZ plasma levels
were measured by a fluorescence polarization immuno-
assay (FPIA) with an automatic analyzer (TDx
Analyzer; Abbott, Wiesbaden, Germany). The
cholesterol precur- sor lathosterol was determined in a
subpopulation by gas chromatography, described
elsewhere (23). Statistical analysis was performed with
the SPSS statistics soft- ware package (SPPS Inc.,
Chicago, IL, U.S.A.). The means of all lipoproteins
were compared with Student’s test for independent
samples. Correlation analysis was performed with
Pearson’ s correlation coefficient and tested for
statistical significance. Subgroup analysis on HDL
cholesterol was performed with an one-way analy- sis of
variance (ANOVA) followed by a post hoc analy- Sis.
RESULTS
Lipoprotein concentrations in female and male pa-
tients and their respective controls are summarized in
Table 2. Serum lipoproteins in controls showed the well-
known sex differences [i.e., no difference in total cho-
lesterol between sexes, but in male subjects, higher LDL
cholesterol (p < 0.01), triglycerides (p < 0.05), and lower
HDL cholesterol (p < 0.001) concentrations]. In CBZ-
treated patients, total, LDL, and HDL cholesterol were
significantly higher in both sexes when compared with
controls (p < 0.001). The differences were more pro-
nounced in women than in men (total cholesterol, 31 vs.
15%, LDL, 38 vs. 17%; HDL, 27 vs. 16%). The propor-
tion of subjects with total cholesterol >240 mg/dl was
59% in CBZ-treated patients and 21% in control subjects
(p < 0.001). Similar proportions were found with LDL
cholesterol >140 mg/dl (60 vs. 36%; p < 0.001). A gen-
der-related analysis showed no difference for both total
cholesterol (CBZ-treated subjects: women, 61%; men,
58%; NS) and LDL cholesterol (CBZ-treated subjects:
women, 63%; men, 699c; NS) in excess. Women treated
with CBZ had slightly higher total cholesterol levels than
men (+8' o, p < 0.05), whereas there was no difference in
LDL cholesterol. The concentrations of triglycerides
were not altered by CBZ. The increase in LDL choles-
terol levels to the means of the corresponding control
groups was more pronounced in CBZ-treated women
than in men (+38% in women vs. +17% in men; p <
0.001). This difference in increase also was visible for
HDL cholesterol but was not so pronounced (+27% in
women vs. +17% in men; p < 0.05). The prognostically
important LDL-to-HDL cholesterol ratio showed the
well-known gender difference in CBZ-treated subjects
(2.3 + 0.9 in women vs. 3.2 + 1.1 in men; p < 0.001) as

TABLE 2. Lif›uprotein concentrations in patients treated with carbamazepine

and controls
Women Men
Carbamazepine Control Carbamazepine Control
(n = 56) (n — 67) (n — 71) (n = 11(I)
Total cholesterol 259 + 56 197*40“ 239 + 42’ 207 + 42‘
LDL cht›lesterol 160 +45 116 +41“ 157*37 134 41"‘
HDL cholesterol 76 + 25 60* 17“ 52 + 14‘ 45 + 12"’
Triglycerides 116*91 102*50 153* 73" 141 + 74“

Values expressed as mg/d1 (mean + SD).

LDL, low-density lipoprotein; HDL, high-density lipoprotein.
“ Significant difference between carbamazepine and control group (p < 0.001). Significant
differences between male and female carbamazepine groups (‘p < 0.05; ‘p < 0.00J ).
Signifi- cant differences between male and temale control groups (“p < 0.05; ‘p < 0.01;
p < 0.001).
Ep'ilepz ia, Vol. 40, No. 4, 1999
4fil2 T. SUDHOP ET AL.

FIG. 1. High-density lipoprotein distri-

bution in patients treated with carba-
mazepine.

15 25 35 45 55 65 75 85 95
HDL cholesterol
Class means (mg/dI]

well as in the control groups (2.2 + 1 .1 in women vs. 3.3 investigators reported an increase in HDL cholesterol;
+ I .6 in men; p < 0.001). Treatment with CBZ did not increased concentrations of total cholesterol were only
alter this ratio significantly in either male or female pa-
rarely observed (2,4,6). Findings in LDL levels also are
tients. Most CBZ-treated men showed HDL cholesterol
controversial. Most studies demonstrated increased LDL
levels between 40 and 60 mg/dl; only one patient ex-
cholesterol levels during CBZ treatment (4,9,28),
ceeded 95 mg/dl. However, 19% of the CBZ-treated
whereas in other studies, these findings could not be
women showed HDL cholesterol levels >95 mg/d1 (Fig.
confirmed (3,7).
I ). The comparison of HDL cholesterol levels with daily
Only a few studies evaluated possible gender-related
dosage of CBZ, analyzed in quintiles, revealed no dif-
differences of serum lipid levels. Calandre et al. (3) re-
ference between the five dose subgroups in both women
ported results in 34 patients with epilepsy ( 18 women,
and men (Table 3). Further to analy ze the possible
16 men) treated with CBZ. In this study, significantly
mechanism of influence of CBZ on cholesterol synthesis,
lower plasma levels of HDL cholesterol were found, but
we measured the cholesterol precursor lathosterol and
total cholesterol levels remained unchanged. However, a
calculated the ratio of lathosterol to cholesterol in those
sex difference could not be demonstrated. Hindi et al.
26 patients treated with CBZ, who demonstrated very
(28) examined 79 patients with epilepsy (31 women and
high or very low HDL cholesterol levels (Table 3). Nei-
48 men) and healthy controls. In a gender-related
ther 1athosterol concentrations nor the lathosterol/
subgroup analysis, increased LDL levels could be
cholesterol ratio, an indicator of the hepatic cholesterol
synthesis (24), revealed significant differences between observed only in female patients, whereas increased
the subgroups (i.e., controls and persons treated with HDL concentrations were demonstrated only in male
CBZ). No significant correlations between duration of patients. Results of a prospective study, performed by
CBZ treatment and lipid parameters (total, LDL, and lsojarvi et al. (4) in 21 men and 15 women with epilepsy,
HDL cholesterol, triglycerides, lathosterol, and lathos- support our findings.
terol-to-cholesterol ratio) could be observed, either for
the pooled analysis of all CBZ-treated subjects or for a
gender-related subgroup analysis. TABLE 3. HDL ‹ Celeste rel in carbumazeg inc dose quintiles
HDL Cholesterol
DISCUSSION mg/d1 (mean SD)
Carbainazepine dose
quintiles (mg/day) \Vomen Men
As a result of this study, we were able to demonstrate
that patients with focal epilepsies treated with CBZ show 200—700 (n = 25) 66 + 17 (n = 15) 48* 13 (n 1())
75a I ,000 (n — 28) 85 * 26 (n = 11) TO * 12 (n = 17)
elevated LDL and HDL cholesterol levels. Similar in-
vestigations in adults and children with epilepsy, previ- 1,200-l,350 (n — 22) 81 z 23 (n = 11) ñ5 + 2U (n = 11)
ously reported by others (2—4,6,7,9,25-27), demon- 1,4f)0— I ,6t)0 (n — 23) 80 + 33 (n = 12) J3 + 14 (n = 21)
strated identic-u1 as well as controversial results. Most 1,800 3,000 (n = 19) 7ñ + 27 (n = 7) ñ3 + I I (n = 12)

None of the five groups showed significant difference in HDI cho-

lesterol.
H DL, high-density lipoprotein.
 SEX DIFFERENT.ES IN HDL WITH CARBAMAZEPINE
Paket dan harga jasa translate AULIA and TEAM yang
*TERBARU* :
Kedokteran dan NON kedokteran.
GARANSI REVISI TANPA BATAS....
KILAT (< 24 jam) = 40ribu perhalaman hasil
CITO (1-2 hari) = 25ribu perhalaman hasil
REGULER (3-4 hari) = 20ribu perhalaman hasil
HEMAT (5-7 hari) = 15ribu perhalaman hasil
*Potongan harga di akhir totalan*
Pengerjaan oleh tim jasa translate "AULIA"
*Format halaman jadi hasil Translate :*
📒Kertas A4
📒Margin rata
Kiri 4
Atas 3
Kanan 3
Bawah 3 (cm)
📒spasi 1,5
483
📒Font times new roman, Ukuran 12
⚠️⚠️⚠️
(Format diatas yang akan digunakan untuk mengalikan
dengan biaya translate per-lembarnya, jadi BUKAN halaman
asli jurnal ya yang kami pakai)
Bila tabel/gambar dimasukkan, secara otomatis menambah
jumlah halaman.
*semua free garansi revisi* 🙂To detect possible causative
factors of the HDL cho- lesterol increase in patients treated
with CBZ, we corre- lated the HDL cholesterol
concentrations to CBZ serum levels and measured
lathosterol, one of the precursors of cholesterol, an indicator
of the hepatic cholesterol syn- thesis. However, a dose-
related correlation between HDL cholesterol and CBZ
levels was not found, either in total concentrations of the
CBZ plasma level or in rela- tion to body weight. A
subgroup analysis between CBZ dose quintiles did not reveal
any significant difference in HDL cholesterol (Table 3).
Finally, neither lathosterol nor the lathosterol-to-cholesterol
ratio differed between patients with increased and low
cholesterol levels in both genders (Table 4). Thus we are not
able to give a con- clusive explanation for the observed
alteration of choles- terol metabolism in CBZ-treated
patients. We might speculate that the enzyme-inducing effect
of CBZ on the hepatic microsomal cytochrome P-450 system
might contribute to cholesterol increase. Previous reports ad-
dressed to this possible mechanism: In a study reported by
Luoina et a1. ( 1), only patients with CBZ-related he- patic
enzyme induction developed a significant HDL cholesterol
increase during treatment. Liver enzyme in- duction by CBZ
might cause an increase in HDL cho- lesterol by an increased
synthesis of apolipoprotein A, the main HDL lipoprotein
particle. Increased apolipopro- tein A levels due to decreased
catabolism might contrib- ute to increased HDL serum
concentrations, but in-

creased synthesis of apolipoprotein A might also be an
explanation of these findings (29). Increased
apolipopro- tein A levels have been documented in
patients treated with CBZ (3). Alteration of
apolipoprotein A metabolism could, therefore, be a
possible mechanism in the increase of HDL cholesterol
levels.
Another finding in our study is the higher LDL cho-
lesterol concentration in patients ot both sexes during
CBZ treatment. Again, the explanation for the
increased LDL levels remains to be elucidated. Studies
in persons treated with phenobarbitone OPB; an
enzyme-inducing anticon vulsant drug like CBZ)
documented an enormous increase of the activity of the
cholesterol synthesis rate- limiting enzyme 3-hydroxy-
3-methyl-glutaryl-CoA re- ductase (HMG-CoA
reductase; mean increase from 161
+ 3.4 to 31S * 82 pmol/qg/min; 30). Thus an increase
in LDL levels might (in part) be explained by this
mecha- nism. However, if the increase of HMG-CoA
reductase was the main mechanism of LDL increase,
we would expect a parallel increase in the
lathosterol/cholesterol ratio. As we demonstrated in our
patients, neither lathos- terol nor the
lathosterol/cholesterol ratio was increased. Therefore, it
is not likely that an increase of HMG-CoA reductase is a
relevant mechanism in LDL cholesterol increase in
persons treated with CBZ. Franzoni et a1. (8), who
examined the influence of various antiepileptic drugs
(AEDs) such as CBZ, PB, phenytoin (PHT), and
valproate (VPA), discussed a possible influence of CBZ
on cholesterol metabolism, which might lead to a com-
petition in cholesterol breakdown to bile acids. Thus
CBZ may induce P-450 but, at the same time, it might
also reduce the free P-450 capacity for cholesterol me-
tabolism due to its utilization. This hypothesis might be
supported by our findings insofar as CBZ did not alter
cholesterol synthesis; thus interaction on the level of
cholesterol metabolism to bile acids might be a possible
mechanism of action.
A clinically relevant aspect of the findings might be
the influence of cholesterol levels on the manifestation of
CHD. It is well known that increased HDL cholesterol
levels decrease the risk of death from CHD and that in
untreated populations, women have a lower incidence of
CHD. It is well accepted that, at least in part, the lower

TABLE 4. Luthosterol and rntic› nf lathosterol to chole.sterol in diffei‘ent HDL cholesterol

subgroup.s in patient.s treated w'ith carbama7epine
Women Men
Low HDL-C High HDL-C Low H DL- High HDL-C
(30—56) (102—134) C (20—36) (7 I —59)
(n — 7) (n = 7) (n = S) (n = 3)
Lathosterol (mg/dl) ().30 + 0.25 0.33 + 0.15 0.30 + 0.07 0.26 + 0,09 NS
Lathosterol/Cholesterol (qg/rug) I .31 0.55 1.15 * 0.39 1.57 + 0.27 1.19 + 0.22 NS

Values expressed as mean + SD; HDL cholesterol range (tag/dl).

HDL-C, high-density lipoprotein cholesterol; NS, no significant difference in the analysis of variance.
484 T. SUDHOP ET AL.
incidence in CHD in women is related to increased HDL
cholesterol levels (10,15—17,31). Therefore treatment
with CBZ might contribute to a lower rate of CHD in
patients with epilepsy, as documented in a Finnish study
by Erila, as reported by Luoma (14,32). In this autopsy
study of 1,961 deaths of patients with epilepsy between
1967 and 1973, 189 deaths related to CHD were ob-
served. The CHD mortality was 11.3% in men and 6.59c
in women. This is a significantly lower rate compared
with the complete Finnish population with a CHD mor-
tality rate of 22.9% in men and 14.3% in women. These
data were confirmed by Muuronen et al. (13), who per-
formed an autopsy case—control study in 1,399 AED us
ers who died between 1978 and 1980. The authors re
ported a significantly lower mortality rate of CHD in
AED users compared with age- and sex-matched con-
trols (18.4% vs. 27.3%, p < 0.001). These epidemiologic
data support the importance of lipoprotein cholesterol
alterations by CBZ. To examine the HDL and LDL cho-
lesterol—increasing mechanisms in regard to apolipopro-
tein metabolism, we initiated a prospective study in
healthy volunteers to elucidate the mechanisms of lipo
protein synthesis and catabolism before and during CBZ
treatment.
REFERENCES
1. Luoma PV, Sotaniemi EA, Pelkonen RO, Pirttiaho HI. Serum low-
density lipoprotein and high-density lipoprotein cholesterol, and
liver size in subjects on drugs inducing hepatic microsomal en-
zymes. Eur I Clin Pharmacol 1985;28: 615—8.
2. Brown DW, Ketter TA, Crumlish J, Post RM. Carbamazepine-
induced increases in total serum cholesterol: clinical and theoret-
ical implications. 7 Clin Psychopharmac ol 1992;12:431—7.
3. Calandre EP, Rodriguez-Lopez C, Blazquez A, Cano D. Serum
lipids, lipoproteins and apolipoproteins A and B in epileptic pa-
tients treated with valproic acid, carbamazepine or phenobarbital.
Acta Neurol Scand l991;83:250—3.
4. Isojiirvi JI, Pakarinen AJ, Myllyla VV. Serum lipid levels during
carbamazepine medication: a prospective study. Arch Nevrol 1993;
fi0:590—3.
5. Zeitlhofer I, Doppelbauer A, Tribl G, Leitha T, Deecke L.
Changes of serum lipid patterns during long-term anticonvulsive
treatment. Clin frive.st 1993;71:574—8.
I›. Reddy MN. Effect of anticonvulsant drugs on plasma total choles-
terol, high-density lipoprotein cholesterol, and apolipoproteins A
and B in children with epilepsy. Proc Soc Exp Biol Med 1985;
1 SO:359—63.
7. Heldenberg D, Harel S, Holtzman M, Levtow O, Tamir I. The
effiect ot chronic anticon vulsant therapy on serum lipids and lipo-
proteins in epileptic children. Neurolo g y 1983;33:5 I 0—3.
Franzoni E, Govoni M, D’Addato S, et al. Total cholesterol, high-
density lipoprotein cholesterol, and triglycerides in chi ldren
receiv- ing antiepileptic drugs. Epilef›sia 1992;33:932—5.
9. Eiris JM, Lojo S, Del Rio MC, et a1. Eftects ot long-term
treatment with antiepileptic drugs on serum lipid levels in children
with epilepsy. Neurolo py 1995;4.5: 1155—7.
l() Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S,
Kannel WB. Incidence of coronary heart disease and lipoprotein
cholesterol levels. The Framingham Study. JAMA 1986;256:2835
— S.
11. Assmann G, Funke H. HDL metabolism and atherosclerosis. J
Cardiova.sc Pharmacol 1990; lit(suppl 9):S15—20.
12. Livingston S. Phenytoin and serum cholesterol [Letter]. Br Med I
1976;586:586.
13. Muuronen A, Kaste M, Nikkila EA, Tolppanen EM. Mortality
frrim ischaemic heart disease among• patients using
anticonvulsive drugs: a case-control study. Br Med I Clin Res Ed
1985;29l: 1481— 3.
14. Erila T. Epileptikkojen kuolleisuus Suomessa vuosina 1967— 1973.
[Summary in English: Mortality of patients with epilepsy in Finn-
land 1967— 1973]. Acta Univ T‹imf›eren.sis Ser A 1982; 145: I —
167.
15. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR.
High density lipoprotein as a protective factor against coronary
heart disease: The Framingham Study. Am I Med 1977;62:707—
l4.
16. Anderson KM, Wilson PW, Garrison RJ, Castelli WP. Longitudi-
nal and secular trends in lipoprotein cholesterol measurements in
a general population sample: The Framingham Offspring Study.
Ath- erosclerosis 1987;68:59 66.
l7. Assmann G, Schulte H. The importance of triglycerides: results
from the Prospective Cardiovascular Munster (PROCAM) Study.
Eur J Epidemiol I 992;8(suppl 1):99—103.
18. Isojarvi JI, Pakarinen AJ, Rautio A, Pelkonen O, Myllyla VV.
Liver enzyme induction and serum lipid levels atter replacement
of carbamazepine with oxcarbazepine. Ef›ilepsia 1994;35: 1 217
—20.
19. Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carba-
mazepine metabolism: role of CYP3A4 and CYP2C8 in 10,11-
epoxide formation. Biochem Pharmacol 1994;47: 1969—79.
20. Pirmohaired M, Kitteringham NR, Breckenridge AM, Park BK.
The effect of enzyme induction on the cytochrome P450-
mediated bioactivation of carbamazepine by mouse liver
microsomes. Bio- chem Pharmacol 1992;44:2307—14.
21. Pirmohamed M, Kitteringham NR, Guenthner TM, Breckenridge
AM, Park BK. An investigation of the formation of cytotoxic,
protein-reactive and stable metabolites from carbamazepine in
vitro. Biochem Pharmacol 1992;43: 1675-82.
22. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the con-
centration of low-density lipoprotein cholesterol in plasma, with-
out use of the preparative ultracentrifuge. Clin Chem 1972;
18:499— 502.
23. Heinemann T, Kullak Ublick GA, Pietruck B, von Bergmann K.
Mechanisms of action of plant sterols on inhibition of cholesterol
absorption: comparison of sitosterol and sitostanol. £«r I Clin
Pharmacol 1991;40(suppl 1):S59—63.
Bjoi‘khem I, Miettinen T, Reihner E, Ewerth S, Angelic B, Ein-
arsson K. Correlation between serum levels of .some cholesterol
precursors and activity of HMG-CoA reductase in human liver. 7
Lipid Res 19S7;28: 1137W3.
25. Yalcin E, Hassanzadeh A, Mawlud K. The effects of long-term
anticonvulsive treatment on serum lipid profile. Acta Paedialr
Jpn 1997;39: 342—5.
26. Verrotti A, Domizio S, Angelozzi B, Sabatino G, Morgese G,
Chiarelli F. Changes in serum lipids and lipoproteins in epileptic
children treated with anticonvulsants. I P‹iedi‹itr Child I-lealth
1997;33:242—5.
27. Sozuer DT, Atakil D, Dogu O, Baybas S, Arpaci B. Serum lipids
in epileptic children treated with carbamazepine and valproate.
Eur I Pediatr 1997;156:565—7.
28. Hindi AJ, Al-Shamma GA, Al-Jadiry AMH, Zaidan ZAJ, Al-
Hussainy T. Serum lipids in epileptic patients receiving carbamaz-
epine; et feet of age, sex and serum concentration. Med S6'i Re.s
1989;17: 155-6.
29. Brinton EA, Eisenberg S, Breslow JL. Elevated high density lipo-
protein cholesterol levels correlate with decreased apolipoprotein
A-1 and A-11 fractional catabolic rate in women. 7 Clin Invest
l989;84: 262—9.
Coyne MJ, Bonorris GG, Goldstein LI, Schoenfield LJ. Effect of
chenodeoxycholic acid and phenobarbital on the rate-limiting en-
zymes of hepatic cholesterol and bite acid synthesis in patients
with g’allstones. J Lab Clin Med l976;87:281—91.
31. Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentra-
tion and development of ischaemic heart-disease. Lancet 1975;1:
16—9.
E fiiley.si i, Ve 1. 40, No. 4, / 999
32. Luoma PV. Microsomal enzyme induction, lipoproteins and ath-
erosclerosis. Pharmacol Toxicol 1988;62:243—9.