THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 11, Number 6, 2005, pp. 1031–1038 Mary Ann Liebert, Inc.
Plasma Clearance of Lovastatin Versus Chinese
ZHAOPING LI, Ph.D., M.D., NAVINDRA P. SEERAM, Ph.D., RUPO LEE, M.Sc., GAIL THAMES, B.A.,
CHAYO MINUTTI, HE-JING WANG, M.P.H., M.D., and DAVID HEBER, Ph.D., M.D. ABSTRACT Objectives: It is now accepted that inhibition of cholesterol biosynthesis is effective in the primary and sec-
ondary prevention of heart disease. However, the perceived side-effects on muscle and liver reduce the generalacceptance of statin drug therapy as well as compliance over the long term, which is necessary for preventionefforts to be successful. Chinese red yeast rice (CRYR) is a supplement containing lovastatin (monacolin K),eight other monacolins, pigments, tannins, and other phytochemicals. The authors previously reported on a dou-ble-blind placebo-controlled trial of CRYR supplement in 80 individuals demonstrating a significant decreasein cholesterol levels from 250 mg/dL to 210 mg/dL over 8 weeks independent of diet. The current study com-pared the pharmacokinetics of CRYR with lovastatin at the same bioeffective dose for lowering cholesterol. Methods: Eleven (11) healthy volunteers were randomized to a crossover study taking 2400 mg CRYR or Results: The Cmax and area under the curve (AUC) of lovastatin were 22.42 ng/mL, and 80.47 higher than
CRYR (p ϭ 0.001 and 0.002, respectively). The Cmax for lovastatin hydroxy-acid was 36.63 ng/mL higher thanthe Cmax of CRYR hydroxy-acid (p ϭ 0.001). The AUC of lovastatin hydroxy-acid was 258.5 greater than thatof CRYR (p ϭ 0.001). Conclusions: The results suggested that the effect of CRYR on the cholesterol concentration might be caused
by the additive and/or synergistic effects of monacolin K with other monacolins and substances in CRYR. Itmay lead to the ultimate development of a botanical supplement based on CRYR. INTRODUCTION
prevention rather than taking drugs,2,3 and view these as nat-ural alternatives to drug therapy. It is now accepted that inhibition of cholesterol biosyn- Chinese red yeast fermented on rice is a traditional food
thesis is effective in the primary and secondary preven-
consumed throughout Asia. Its food value and medicinal value
tion of heart disease. Statin drugs, which are competitive in-
date back prior to its first recorded use in 800 AD.4,5 A die-
hibitors of HMG-CoA reductase, lower cholesterol levels
tary supplement of Chinese red yeast rice (CRYR) has been
and reduce the progression of atherosclerotic lesions while
prepared that contains only a selected strain of Monascus pur-
also stabilizing pre-existing atheromatous plaques. The per-
pureus Went yeast and white rice on which it was fermented.
ceived side-effects on muscle and liver reduce the general
There are a number of constituents in the supplement includ-
acceptance of statin drug therapy as well as compliance over
ing pigments, fatty acids, and polyketides (monacolins).6
the long term, which are necessary for prevention efforts to
The authors previously reported on a double-blinded
be successful.1 Surveys demonstrate that many Americans
placebo-controlled trial of this CRYR supplement in 80 in-
often turn to alternative herbal therapies for heart disease
dividuals demonstrating a significant decrease in cholesterol
Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA.
TABLE 1. CONSTITUENTS OF CHINESE RED YEAST RICE
by inhibiting CYP3A4-mediated first-pass metabolism in
the small intestine. The present study uses the preceding
method to increase the detectable levels of monacolins.
The subjects were given 200 mL of double-strength
grapefruit juice (Minute Maid frozen concentrated grape-
fruit juice, 12 fluid ounces (355 mL), Coca-Cola Foods,
Houston, TX) three times per day (at 7 AM, noon, and 8 PM)
for 2 days. On day 3, the subjects reported to the GCRC at
7:30 AM after fasting from 11 PM the previous day. A caf-
feine-free standardized breakfast was served at 7:45 AM and
either 20 mg of lovastatin or 2400 mg of Chinese red yeast
rice was given with 200 mL of double-strength grapefruit
juice at 8 AM. Standardized lunch and dinner were served at
noon and 5 pm. The subjects returned to the GCRC the next
morning to have their blood last drawn at 8 AM.
On the day of administration of lovastatin or CRYR, a
forearm vein of each subject was cannulated with a plasticcannula and kept patent with a heparin flush. Blood sam-
levels from 250 mg/dL to 210 mg/dL over 8 weeks inde-
ples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24
pendent of diet.7 The current study was designed to com-
hours after taking lovastatin or taking CRYR. Whole blood
pare the pharmacokinetics of CRYR with lovastatin at the
was centrifuged immediately and plasma transferred to plas-
same bioeffective dose for lowering cholesterol to determine
tic tubes and frozen at Ϫ80°C until assay.
whether the body metabolizes complex mixtures of naturalsubstances found in CRYR differently than lovastatin. Methodology for determination of monacolin K (lovastatin) and lovastatin hydroxy-acid in human plasma
Lovastatin 20–mg capsules were purchased from Merck
& Co. Inc. (Whitehouse, NJ) CRYR dietary supplement 600-
mg capsules were provided by Beijing WBL Peking Uni-
The study protocol was approved by the Ethics Commit-
tee of the University of California, Los Angeles and con-
HPLC-MS analyses were carried out on an LCQ Classic
ducted at the General Clinical Research Unit (GCRC) of
Finnigan LC-MS/MS system (ThermoFinnigan, San Jose,
University of California, Los Angeles. Eleven (11) volun-
CA), equipped with a HP 1100 series HPLC system consist-
teers ages 25 to 45 year were recruited for the study. Writ-
ing of an autosampler and injector, quaternary pump, column
ten consent was obtained. All participants were in goodhealth according to medical history, physical examination,electrocardiogram, and clinical laboratory measurements
(serum chemistry, liver function tests, and hematology).
Subjects were excluded if they were smokers, tobacco users,or taking any medication including over-the-counter med-
ications within 14 days prior to the study.
This was an open label, randomized, crossover study with
a 1-week washout period between two phases. The previousstudy had demonstrated that 2400 mg of CRYR is a rele-
High performance liquid chromatography trace of mona-
vant comparison dose to 20 mg of lovastatin for lowering
colins. 1, Monacolin Kanalogue; 2, Monacolin K dehydro ana-
logue; 3, Hydroxy-acid form of Monacolin L; 4, Hydroxy-acid form of Monacolin K; 5, Dihydromonacolin K; 6, Monacolin L;
Kantola et al.8 reported that grapefruit increased the
7, Hydroxy-acid form of dehydromonacolin K; 8, Monacolin K; 9,
serum levels of lovastatin (Cmax) approximately 12-fold and
Methyl ester of hydroxy-acid form of monacolin K; 10, Dehy-
the area under the concentration-time curve (AUC) 15-fold
LOVASTATIN VERSUS RED YEAST RICE
#143-147 RT: 0.78-0.80 AV: 5 NL: 1.74E6F: +p Full ms2 427.20@35.00[115.00-500.00]
K acid #57 RT: 0.59 AV: 1 NL: 2.96E5T: −p Full ms2 421.30@30.00 [115.00-500.00]
sim #72-74 RT: 0.38-0.40 AV: 3 NL: 1.53E6T: +p Full ms2 441.20@35.00 [120.00-500.00]
MA); Solvent A) 0.5% acetic acid/acetonitrile, B) 0.5% acetic
acid/water; binary linear gradient system: 0–15 min: 50% A
in B to 90% A in B; 15–18 min, 90% A in B; flow rate 0.2
mL/minute; injection volume 20 L; column temperature
25°C. Mass spectrometer (MS) parameters: The MS (elec-
trospray ionization; ESI) was operated in the negative mode
for the first 11 minutes and then in the positive mode for the
rest of the analytical run; scan range: 115–500 amu; scan rate:
1 scan/sec; cone voltage: 17 eV. Peak identities for lovastatin,
lovastatin hydroxy-acid, and simvastatin were obtained by
comparison of their LC-MS/MS ions with their standards.
Each C8 SPE cartridge was preconditioned with methanol
(2 ϫ 1 mL) and water (2 ϫ 1 mL). Each plasma sample
(400 L) was loaded onto the cartridge and allowed to free-
flow by gravity. Each cartridge was then eluted with con-
secutive aliquots of 1 mL water, 1 mL 5% formic acid, and
then 1 mL of water. The cartridge was allowed to drip dry,
left to stand for 1 minute, then eluted with 1 mL methanol:water (7:3 v/v) solution, and finally with 1 mL of acetoni-
A. Liquid chromatography-mass spectrometry (LCMS)
trace of lovastatin (monacolin K) standard. The molecular ion is
trile. The combined acetonitrile eluates were evaporated to
at m/z 427 ϭ [M ϩ Na]ϩ as reported.9 B. LCMS trace of lovas-
dryness in vacuo at low temperature, reconstituted in the
tatin (monacolin K) hydroxy-acid standard. The molecular ion at
HPLC mobile phase (100 L), vortexed for 1 minute, and
m/z 421 ϭ [M–H]Ϫ as reported.9 C. LCMS trace of simvastatin
injected onto the LC column for LC-MS analyses.
standard. The molecular ion is at m/z 441 ϭ [M ϩ Na]ϩ as re-
Plasma calibration standards of lovastatin and its hy-
droxy-acid were prepared by spiking control human plasmawith known concentrations of working solutions of the stan-
heater, and diode array detector (DAD). Data handling was
dards. Samples were processed according to the extraction
carried out using Xcalibur 1.2 software (ThermoFinnigan).
procedure and injected on to the HPLC-MS. Concentrations
Conditions for detection were as follows: Column, Symme-
were determined from the peak area by using the equation
try C-18, 100 mm ϫ 2.1 i.d., 3.5 m, (Waters Corp., Milford,
for linear regression obtained from the calibration curve. The
calibration curve was linear (R2 ϭ 0.9954 for lovastatin and
0.9927 for lovastatin hydroxy-acid, respectively) over the
The mean values and pharmacokinetics for lovastatin and
concentration range from 0.1 to 100 ng/mL. The lower level
CRYR are summarized in Table 2 and the mean plasma con-
of quantitation (LOQ) established from the calibration curve
centration versus time profiles for monacolin K and mona-
by LCMS was 0.1 ng/mL based on 400 L of plasma. Sim-
colin K hydroxy-acid are shown in Figures 4A,B, respec-
vastatin was used as an internal standard as previously re-
tively. Monacolin K was detected in plasma 30 minutes after
ingestion of either lovastatin or CRYR. The peak concen-tration reached at approximately 3 hours. The Cmax and AUC
of lovastatin are 22.42 ng/mL, and 80.47 higher than CRYR
The pharmacokinetic parameters, peak plasma concen-
with p value of 0.001 and 0.002, respectively. The dose-nor-
malized Cmax and AUC of lovastatin are 0.89 ϩ 0.22 ng/mL,
max), time to peak plasma concentration (Tmax),
and time for appearance of the drug in plasma were obtained
and 3.41 ϩ 0.99 higher than CRYR with p value of 0.001
by observation. The AUC from 0 to 24 hours after dosing
was calculated by the linear trapezoidal rule. Elimination
Monacolin K hydroxy-acid was detected 30 minutes af-
ter taking lovastatin or CRYR but peaked at 4 hours, 1 hour
1/2) was estimated by 0.693/, where is the ab-
solute value of the slope of a least-square linear regression
later than when monacolin K peaked. The Tmax for lovas-
of plasma drug concentration (in natural logarithm scale)
tatin and CRYR hydroxy-acids were similar (p ϭ 1.00,
signed rank test). The Cmax for loavstatin hydroxy-acid is
The pharmacokinetic parameters of lovastatin and lovas-
36.63 ng/mL higher than the Cmax of CRYR hydroxy-acid
tatin hydroxy-acid were tabulated using mean Ϯ SEM for
(p ϭ 0.001, signed rank test). The AUC of lovastatin hy-
taking lovastatin and CRYR, respectively. This was a 2-by-
droxy-acid is 258.5 larger than that of CRYR (p ϭ 0.001).
2 crossover study with 7-day washout period. No carryover
After normalization for dose, the AUC of lovastatin is still
effect was identified, and no significant period and sequence
7.21 larger than that of CRYR (p ϭ 0.001).
effects were found; therefore, signed rank test was used to
The individual sample for minor monacolins were not de-
compare the pharmacokinetic parameters for Lovastatin ver-
tectable by LC-MS/MS. However, the pooled plasma sam-
ples collected from three subjects showed the presence of
All tests used were two sided with a significance level of
minor monacolins reported to be present in CRYR.10 Sam-
0.05. Statistical software SAS was used to carry out theanalysis. Characterization of the constituents of CRYR
This botanical dietary supplement consists mainly of rice,
and by-products of fermentation. The main groups of con-
stituents are shown in Table 1. Clearly the most abundant
ingredient is starch, constituting over 73% of the bulk. The
protein content is 6%. The other ingredients are found in
much less quantity. Trace elements were analyzed by atomic
absorption spectroscopy. Magnesium is the most abundant
metal with 1094 g/g of rice.
The typical HPLC trace for the monacolin mixture as
found in CRYR is shown in Figure 1 and the Liquid Chro-
matography—Mass Spectrometry (LC-MS) traces of mona-
colin K, monacolin K hydroxyl-acid, and simvastatin stan-
dards are shown in Figures 2A–C, respectively. Figure 3
shows the LC-MS trace of a plasma sample obtained froma human subject with simvastatin added as internal standard
LCMS trace of human plasma sample showing mona-
where monacolin K and monacolin K hydroxy-acid were de-
colin K hydroxy-acid (tr ϭ 9.47 min, base peak m/z 319.06 frommolecular ion at m/z 421); Monacolin K (t
tected. There is 1.23 mg of monacolin K in every capsule
m/z 325.24 from molecular ion at m/z 427); Simvastatin (tr ϭ 14.46
by assay of manufacture and 1.15 mg by HPLC analyses
min, base peak at m/z 325.12 from molecular ion at m/z 441.3) ac-
LOVASTATIN VERSUS RED YEAST RICE
ples from all subjects were analyzed after pooled with two
429)ϩ, monacolin L (tR 13.28 min; M ϩ Na, m/z 327)ϩ, and
subjects. All the analysis showed the same pattern of minor
dehydromonacolin K (tR 18.90 min; M ϩ Na, m/z 409). Fig-
monacolins. The data from one analysis are shown in Fig-
ure 6B shows the LCMS trace of pooled plasma sample with
ures 5 and 6. Because of the unavailability of standards for
ions corresponding to dehydromonacolin K (tR 18.82 min;
these minor monacolins, Selected Ion Monitoring (SIM) was
conducted in negative and positive ESI modes of CRYR,and then followed by MS-MS analyses of ions correspond-ing to each monacolin peak (Figs. 5 and 6). Peak identities
DISCUSSION
were obtained by matching their molecular ions (M Ϫ H)Ϫor (M ϩ Na)ϩ obtained by ES-MS/MS ions with expected
In 1979, Endo11 reported that a strain of Monascus yeast
values.10 Figure 5A shows the LCMS trace of the CRYR
naturally produces a substance that inhibits cholesterol syn-
extract in negative mode with corresponding MS/MS ions
thesis, which he named monacolin K, as well as a family
for monacolin K hydroxy-acid (tR 11.38 min; M Ϫ H m/z
of eight monacolin-related substances with the ability to in-
421), dehydromonacolin K hydroxy-acid (tR 8.36 min; M Ϫ
hibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
H m/z 403), monacolin L hydroxy-acid (tR 9.49 min; M Ϫ
reductase. In addition to the inhibitors of HMG-CoA re-
H m/z 321) and dihydromonacolin K hydroxy-acid (tR 14.10
ductase, red yeast rice has been found to contain sterols
min; M Ϫ H m/z 423). Figure 5B shows the LCMS trace of
(-sitosterol, campesterol, and stigmasterol), tannins, poly-
the pooled human plasma sample with ions corresponding
ketide pigments, sapogenin, isoflavones and isoflavone gly-
to monacolin L hydroxy-acid (tR 9.49 min; M Ϫ H m/z 423)
cosides, and monounsaturated fatty acids.11,12
and dihydromonacolin K hydroxy-acid (tR 14.09 min; M Ϫ
CRYR has been shown to lower cholesterol in animals
H m/z 423). Similarly, Figure 6A shows the LCMS trace of
fed diets designed to induce hypercholesterolemia.13,14 In a
the CRYR extract in positive mode with corresponding
double-blind placebo-controlled and diet-controlled study,
MS/MS ions for monacolin K (tR 14.47 min; M ϩ Na, m/z
CRYR was demonstrated to lower serum cholesterol by 23%
427)ϩ, dihydromonacolin K (tR 17.26 min; M ϩ Na, m/z
in 40 hypercholesterolemic patients compared to 40 patients
A. Plasma concentration versus time profile for monacolin K. B. Plasma concentration versus time profile for monacolin K A. Selected ion monitoring (SIM) spectra of the Chinese red yeast rice (CRYR) extract in negative mode with correspond-
ing MS/MS ions for monacolin K hydroxy-acid (tR 11.38 min; M Ϫ H m/z 421), dehydromonacolin K hydroxy-acid (tR 8.36 min; M Ϫ H m/z 403), monacolin L hydroxy-acid (tR 9.49 min; M Ϫ H m/z 321), and dihydromonacolin K hydroxy-acid (tR 14.10 min; M–H m/z 423). B. SIM spectra of the pooled human plasma sample with corresponding MS/MS iosn for monacolin L hydroxy-acid (tR 9.49 min; M–H m/z 321) and dihydromonacolin K hydroxy-acid (tR 14.09 min; M–H m/z 423).
15.32 15.70 16.03 16.59 17.42 17.94 18.37 19.08 19.72
14.66 15.19 15.82 16.24 16.7717.33 17.6917.9518.32 19.09 19.43
A. Selected ion monitoring (SIM) spectra of the Chinese red yeast rice (CRYR) extract in positive mode with corresponding
MS/MS ions for monacolin K (tR 14.47 min; M ϩ Naϩ, m/z 427), dihydromonacolin K (tR 17.26 min; M ϩ Naϩ, m/z 429), monacolin L (tR 13.28 min; M ϩ Naϩ, m/z 327), and dehydromonacolin K (tR 18.90 min; M ϩ Naϩ, m/z 409). B. SIM spectra of pooled human plasma sample with ion corresponding to dehydromonacolin K (tR 18.82 min; M ϩ Naϩ, m/z 409). LOVASTATIN VERSUS RED YEAST RICE
given placebo.7 The monacolins in CRYR and drug statins
were updated recently about pharmacologic intervention.
are competitive inhibitors of HMG CoA reductase, the reg-
NCEP is now advocating more aggressive therapy for patients
ulatory enzyme of cholesterol synthesis.15
with high and moderate risks.24 Although it is acknowledged
The current study showed that the quantity of monacolin
that side-effects with statins are rare, there are data indicat-
K contained in CRYR is much lower and is inadequate to
ing that some statins may cause liver function abnormalities
explain the magnitude of cholesterol lowering observed in
and, under certain circumstances, rhabdomyolysis in a dose-
the previous study. The 2400 mg CRYR used in this study
related fashion.25 Combined use of different statins in lower
contains only 4.6 mg, 23% of monacolin K of 20 mg lo-
doses may decrease the incidence of side-effects.
vastatin. The findings of this study demonstrated that theplasma concentrations of monacolin K and its hydroxy-acidform are much higher after ingestion of lovastatin than
CONCLUSIONS
CRYR. The mixture of monacolins and other substances pre-sent in the red yeast rice may have some inhibitory effect
In summary this study demonstrated significantly lower
on cholesterol biosynthesis. Pooled plasma collected from
serum monacolin K level for CRYR compared to equiva-
three subjects showed the presence of additional minor
lent cholesterol-lowering dose of lovastatin. CRYR may
monacolins that are known to be present in red yeast rice.10
serve as a safe and effective natural alternative for people
Various synthetic statins have different degrees of bio-
with modest elevation of cholesterol. The effect of red yeast
logic activity, and it is possible that the family of monacol-
rice on the cholesterol concentration is not caused by mona-
ins in CRYR may have a different profile of cellular or mol-
colin K alone but the combination of monacolin K and other
ecular actions. In the current study the monacolin K to
monacolins, substances in the red yeast rice supplement.
monacolin K hydroxy-acid ratio was 1.72 for lovastatin and3.48 for CRYR, which further suggests possible differentmetabolism. At 72 hours after administration, approximately
ACKNOWLEDGMENTS
83% of lovastatin was excreted in stool and 10% in urine.16Similar studies of the bioavailability and bioactivity of
Funding was supplied by the PHS/Institute of National
CRYR monacolins were not performed previously but
would increase the understanding of the metabolism of thisbotanical dietary supplement.
Whereas the proprietary product used in this study was
REFERENCES
demonstrated to lower cholesterol levels significantly inclinical trials, other products being sold as CRYR dietary
1. Simons LA, Levis G, Simons J. Apparent discontinuation rates
supplements have not undergone similar evaluation. Nine
in patients prescribed lipid-lowering drugs. Med J Aust 1996;
proprietary CRYR supplements were analyzed and it was
found that the total monacolin content can vary from 0% to
2. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alterna-
0.58% w/w, only 1/9 preparations had the full complement
tive medicine use in the United States, 1990–1997: Results of
a follow-up national survey. JAMA 1998;280:1569–1575.
Most of the pharmacokinetic data reported for statins in
3. Wootton JC, Sparber A. Surveys of complementary and alter-
native medicine: Part I. General trends and demographic
the literature have been generated using the HMG-CoA re-
groups. J Altern Complement Med 2001;7:195–208.
ductase assay to determine total and active inhibitors of
4. Havel RJ. Dietary supplement or drug? The case of cholestin.
HMG-CoA reductase.18 Although this enzymatic method
can determine the entire latent and active drug and metabo-
5. Stuart MD. Chinese materia medica: Vegetable kingdom.
lites of lovastatin, it is not chemically specific. In contrast,
Taipai, Republic of China: Southern Materials Center, 1979.
the LC-MS/MS method used for determining plasma drug
6. Martinkova L, Patakova-Juzlova P, Krent V, et al. Biological
concentrations in this study is more sensitive and spe-
activities of oligoketide pigments of Monascus purpureus.
cific.9,19 By using LC-MS/MS methodology, lovastatin was
detectable a half hour after the 20-mg dose was adminis-
7. Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go
VL. Cholesterol-lowering effects of a proprietary Chinese
The benefits of statin drugs on the primary prevention of
red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69:231–236.
heart disease20,21 and in the secondary prevention of recur-
8. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly
rent heart disease22,23 have been shown in several large,
increases serum concentrations of lovastatin and lovastatin
prospective clinical trials. These studies have increased in-
acid. Clin Pharmacol Ther 1998;63:397–402.
terest in the prophylactic use of statins for heart disease pre-
9. Wu Y, Zhao J, Henion J, Korfmacher WA, Lapiguera AP, Lin
vention for individuals with hypercholesterolemia. The Na-
CC. Microsample determination of lovastatin and its hydroxy
tional Cholesterol Education Program (NCEP) guidelines
acid metabolite in mouse and rat plasma by liquid chro-
matography/ionspray tandem mass spectrometry. J Mass Spec-
dosage form (Lovastatin XL) in healthy volunteers. Biopharm
10. Ma J, Li Y, Ye Q, et al. Constituents of red yeast rice, a tra-
20. Downs JR, Clearfield M, Weis S, et al. Primary prevention of
ditional Chinese food and medicine. J Agric Food Chem 2000;
acute coronary events with lovastatin in men and women with
average cholesterol levels: Results of AFCAPS/TexCAPS.
11. Endo A. Monacolin K: A new hypocholesterolemic agent pro-
Air Force/Texas Coronary Atherosclerosis Prevention Study.
duced by a Monascus species. J Antibiot (Tokyo) 1979;32:
21. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary
12. Wu LC, Chen YC, Ho JA, Yang CS. Inhibitory effect of
heart disease with pravastatin in men with hypercholes-
red koji extracts on mushroom tyrosinase. J Agric Food Chem
terolemia. West of Scotland Coronary Prevention Study
Group. N Engl J Med 1995;333:1301–1307.
13. Wei W, Li C, Wang Y, Su H, Zhu J, Kritchevsky D. Hypo-
22. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravas-
lipidemic and anti-atherogenic effects of long-term Cholestin
tatin on coronary events after myocardial infarction in patients
(Monascus purpureus–fermented rice, red yeast rice) in cho-
with average cholesterol levels. Cholesterol and Recurrent
lesterol fed rabbits. J Nutr Biochem 2003;14:314–318.
Events Trial investigators. N Engl J Med 1996;335:1001–1009.
14. Li C, Zhu Y, Wang Y, Zhu J-S, Chang J, Kritchevsky D.
23. Randomised trial of cholesterol lowering in 4444 patients with
Monascus purpureus–fermented rice (red yeast rice): A nat-
coronary heart disease: The Scandinavian Simvastatin Survival
ural food product that lowers blood cholesterol in animal mod-
Study (4S). Lancet 1994;344:1383–1389.
els of hypercholesterolemia. Nutrition Res 1998;18:71–81.
24. Grundy SM, Cleeman JI, Merz CN, et al. Implications of re-
15. Edwards PA, Popjak G, Fogelman AM, Edmond J. Control of
cent clinical trials for the National Cholesterol Education Pro-
3-hydroxy-3-methylglutaryl coenzyme A reductase by en-
gram Adult Treatment Panel III Guidelines. J Am Coll Car-
dogenously synthesized sterols in vitro and in vivo. J Biol
25. Bellosta S, Paoletti R, Corsini A. Safety of statins: Focus on
16. Duggan DE, Chen IW, Bayne WF, et al. The physiological dis-
clinical pharmacokinetics and drug interactions. Circulation
position of lovastatin. Drug Metab Dispos 1989;17:166–173.
17. Heber D, Lembertas A, Lu QY, Bowerman S, Go VL. An
analysis of nine proprietary Chinese red yeast rice dietary sup-
plements: Implications of variability in chemical profile and
contents. J Altern Complement Med 2001;7:133–139.
18. Erturk S, Onal A, Muge CS. Analytical methods for the quan-
titative determination of 3-hydroxy-3-methylglutaryl coen-
University of California, Los Angeles
zyme A reductase inhibitors in biological samples. J Chro-
matogr B Analyt Technol Biomed Life Sci 2003;793:193–205.
19. Lamson M, Phillips G, Shen J, Lukacsko P, Friedhoff L, Niece-
stro RM. Pharmacokinetics of lovastatin extended-release
PATIENT INFORMATION – HAVING A GASTROSCOPY Patient’s name: ……………………………………………………………………………………………. Your appointment is at Royal Preston Hospital (01772 522032)/Chorley Hospital (01257) 245656 Endoscopy Unit on ……………………………………. at ………………………………………………. Ga
Three PHRI faculty members: Veronique Dartois, PhD, Theresa Chang, PhD and Marila Gennaro, MD secure $11.5 million in NIH grants. Veronique Dartois, PhD Project Title: Lesion-centric imaging and PK-PD of pyrazinamide for TB/HIV co-infection Project Period: 08/01/2013 – 07/31/2017 Total Award: $3,138,294 Abstract: Pyrazinamide is a central anti-tuberculosis drug which is part of most