108
A.M. Qandil et al. / European Journal of Pharmaceutical Sciences 43 (2011) 99–108
hydroxybupropion in hairless guinea pigs. European Journal of Pharmaceutical
Sciences 33, 371–379.
Lindholm, J., 2004. Development and Validation of HPLC Methods for Analytical and
Preparative Purposes: Acta Universitatis Upsaliensis. Ph.D., University of
Uppsala, Uppsala.
drugs in addition to evaluation of its therapeutic efficiency in
improving the lipid profile in a suitable animal models.
Link, J.J., Rohatgi, A., de Lemos, J.A., 2007. HDL cholesterol: physiology,
pathophysiology, and management. Current Problems in Cardiology 32 (5),
268–314.
Luner, P.E., Babu, S.R., Radebaugh, G.W., 1994. The effects of bile salts and lipids on
the physicochemical behavior of gemfibrozil. Pharmaceutical Research 11 (12),
Manninen, V., Elo, M., Frick, M., et al., 1998. Lipid alterations and decline in the
incidence of coronary heart disease in the Helsinki Heart Study. JAMA 260, 641–
651.
Acknowledgments
This work was funded by a grant from the Deanship of Research
at Jordan University of Science and Technology. The authors would
like to convey their sincere thanks to Mr. Eyad Hamzeh and Mr.
Farouk Al-Zogoul for their help.
Manninen, V., Malkonen, M., Eisalo, A., Virtamo, J., Tuomilehto, J., Kuusisto, P., 1982.
Gemfibrozil in the treatment of dyslipidaemia. A 5-year follow-up study. Acta
Medica Scandinavica 668 (Suppl.), 82–87.
References
Martindale: The Complete Drug Reference, 2010a. Clofibrate Retrieved March 7th,
Martindale: The Complete Drug Reference, 2010b. Etofibrate Retrieved March 7th,
Martindale: The Complete Drug Reference, 2010c. Gemfibrozil Retrieved March 7th,
Meyers, C.D., Liu, P., Kamanna, V.S., Kashyap, M.L., 2007. Nicotinic acid induces
secretion of prostaglandin D2 in human macrophages: an in vitro model of the
niacin flush. Atherosclerosis 192 (2), 253–258.
Ramires, J., Mansur, A., Solimene, M., Maranhão, R., Chamone, D., da Luz, P., Pileggi,
F., 1995. Effect of gemfibrozil versus lovastatin on increased serum
lipoprotein(a) levels of patients with hypercholesterolemia. International
Journal of Cardiology 48 (2), 115–120.
Rautio, J., Kumpulainen, H., Heimbach, T., Oliyai, R., Oh, D., Järvinen, T., Savolainen,
J., 2008. Prodrugs: design and clinical applications. Nature Reviews Drug
Discovery 7, 255–270.
Raza, J.A., Babb, J.D., Movahed, A., 2004. Optimal management of hyperlipidemia
inprimary prevention of cardiovascular disease. International Journal of
Cardiology 97 (3), 355–366.
Samson, R.H., 2002. Pharmaceutical initiatives to combat atherosclerosis – what to
do with the good, the bad, and the ugly lipoproteins. Seminars in Vascular
Surgery 15 (4), 204–215.
Shabir, G.A., 2003. Validation of high-performance liquid chromatography methods
for pharmaceutical analysis: understanding the differences and similarities
between validation requirements of the US Food and Drug Administration. The
US Pharmacopeia and the International Conference on Harmonization Journal of
Chromatography A 987 (1–2), 57–66.
Simões, M.F., Valente, E., Rodríguez Gómez, M.J., Anes, E., Constantino, L., 2009.
Lipophilic pyrazinoic acid amide and ester prodrugs stability, activation and
activity against M. tuberculosis. European Journal of Pharmaceutical Sciences 37,
257–263.
Sposito, A.C., Mansur, A.P., Maranhão, R.C., Rodrigues-Sobrinho, C.R.M., Coelho, O.R.,
Ramires, J.A.F., 2001. Etofibrate but not controlled-release niacin decreases LDL
cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects. Brazilian
Journal of Medical and Biological Research 34 (2), 177–182.
Steiner, G., 2005. Fibrates and coronary risk reduction. Atherosclerosis 182 (2), 199–
207.
Superko, H.R., Garrett, B.C., King III, S.B., Momary, K.M., Chronos, N.A., Wood, P.D.,
2009. Effect of combination nicotinic acid and gemfibrozil treatment on
intermediate density lipoprotein, and subclasses of low density lipoprotein
and high density lipoprotein in patients with combined hyperlipidemia.
American Journal of Cardiology 103 (3), 387–392.
Superko, R., Garrett, B., King III, S., Superko, S., 2006. Nicotinic acid and gemfibrozil
combination forthetreatmentof familialcombinedhyperlipidemiaand theeffect
on LDL and HDL subclass distribution. Atherosclerosis Supplements 7 (3), 476.
Taher, T.H., Dzavik, V., Reteff, E.M., Pearson, G.J., Woloschuk, B.L., Francis, G.A., 2002.
Tolerability of statin–fibrate and statin–niacin combination therapy in
dyslipidemic patients at high risk for cardiovascular events. American Journal
of Cardiology 89 (4), 390–394.
Taylor, A.J., Stanek, E.J., 2008. Flushing and the HDL-C response to extended-release
niacin. Journal of Clinical Lipidology 2 (4), 285–288.
Thomas, B., Burgess, J., Coleman, D., Scheffler, N., Jeffcoat, A.R., Dix, K., 1999.
Isolation and identification of novel metabolites of gemfibrozil in rat urine.
Drug Metabolism and Disposition 27 (1), 147–157.
Abdel-Azeem, A.Z., Abdel-Hafez, A.A., El-Karamany, G.S., Farag, H.H., 2009.
Chlorzoxazone esters of some non-steroidal anti-inflammatory (NSAI)
carboxylic acids as mutual prodrugs: design, synthesis, pharmacological
investigations and docking studies. Bioorganic and Medicinal Chemistry 17,
3665–3670.
Birjmohun, R.S., Hutten, B.A., Kastelein, J.J.P., Stroes, E.S.G., 2005. Efficacy and safety
of high-density lipoprotein cholesterol-increasing compounds a meta-analysis
of randomized controlled trials. Journal of the American College of Cardiology
45 (2), 185–197.
Carlson, L.A., 2004. Niaspan, the prolonged release preparation of nicotinic acid
(niacin), the broad-spectrum lipid drug. International Journal of Clinical Practice
58 (7), 706–713.
Carlson, L.A., 2005. Nicotinic acid: the broad-spectrum lipid drug.
Anniversary Review. Journal of Internal Medicine 258 (2), 94–114.
A 50th
Cynkowska, G., Cynkowski, T., Al-Ghananeem, A., Guo, H., Ashtona, P., Crooks, P.A.,
2005. Novel antiglaucoma prodrugs and codrugs of ethacrynic acid. Bioorganic
and Medicinal Chemistry Letters 15, 3524–3527.
Davidson, M.H., 2008. Niacin use and cutaneous flushing: mechanisms and
strategies for prevention. American Journal of Cardiology 101 (8 Suppl. 1),
S14–S19.
Davidson, M.H., Toth, P.P., 2004. Comparative effects of lipid-lowering therapies.
Progress in Cardiovascular Diseases 47 (2), 73–104.
Dean, B.B., Borenstein, J.E., Henning, J.M., Knight, K., Merz, C.N.B., 2004. Can change
in high-density lipoprotein cholesterol levels reduce cardiovascular risk?
American Heart Journal 147 (6), 966–976.
Dhaneshwar, S.S., Kandpal, M., Vadnerkar, G., Rathi, B., Kadam, S.S., 2007. Synthesis,
kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-
aminosalicylic acid for colon-specific drug delivery inflammatory bowel
disease. European Journal of Medicinal Chemistry 42, 885–890.
Ermer, J., Miller, J.H.M., 2005. Method Validation in Pharmaceutical Analysis, A
Guide to Best Practice. Wiley-VCH Verlag GmbH, Heppenheim.
FDA (Cartographer), 2001. Guidance for Industry Bioanalytical Method Validation.
Retrieved
from
Ganji, S.H., Kamanna, V.S., Kashyap, M.L., 2003. Niacin and cholesterol: role in
cardiovascular disease. Journal of Nutritional Biochemistry 14 (6), 298–305.
Gurakar, A., Hoeg, J.M., Kostner, G., Papadopoulos, N.M., Brewer Jr., H.B., 1985. Levels
of lipoprotein Lp(a) decline with neomycin and niacin treatment.
Atherosclerosis 57 (2–3), 293–301.
Hamad, M.O., Kiptoo, P.K., Stinchcomb, A.L., Crooks, P.A., 2006. Synthesis and
hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6[beta]-
naltrexol with hydroxybupropion as potential alcohol abuse and smoking
cessation agents. Bioorganic and Medicinal Chemistry 14 (20), 7051–7061.
}
Hassan, H.B., Kata, M., Eros, I., Aigner, Z., 2004. Preparation and investigation of
inclusion complexes containing Gemfibrozil and DIMEB. Journal of Inclusion
Herrera, E., Lasuncion, M.A., Castro, M., Gomez Coronado, D., Martin, A., Quack, G.,
1988. Studies with etofibrate in the rat. Part I: effects on glycerol, free fatty acid
and triacylglycerol metabolism. Biochimica et Biophysica Acta 963 (1), 42–52.
International Conference on Harmonisation, 1997. Guidance for Industry, Q2B
International Conference on Harmonisation, 2005. Validation of Analytical
IPCS Inchem, 1995. Nicotinic acid (CAS No: 59-67-6). Retrieved from http://
Karnes, H.T., March, C., 1993. Precision, accuracy, and data acceptance criteria in
biopharmaceutical analysis. Pharmaceutical Research 10 (10), 1420–1426.
Kashyap, M.L., 1984. The effect of gemfibrozil on plasma lipids and lipoproteins in
man. Vascular Medicine 2, 16–21.
Todd, P.A., Ward, A., 1988. Gemfibrozil. A review of its pharmacodynamic and
pharmacokinetic properties, and therapeutic use in dyslipidaemia. Drugs 36 (3),
314–339.
Yalkowsky, S.H., Morozowich, W., 1980. The physical chemical basis for the design
of orally active prodrugs. In: Aridns, E.J. (Ed.), Drug Design (vol. IX). Academic
Press, New York.
Zema, M.J., 2010. Gemfibrozil, nicotinic acid and combination therapy in patients
with isolated hypoalphalipoproteinemia: a randomized, open label, crossover
study. Journal of the American College of Cardiology 35 (3), 640–646.
Zovko, M., Barbaric, M., Zorc, B., Hafner, A., Filipovic-Grcic, J., 2005. Synthesis of
fenoprofen and gemfibrozil styrene-maleic acid copolymer conjugates. Acta
Pharmaceutica 55, 169–176.
Kiptoo, P.K., Hamad, M.O., Crooks, P.A., Stinchcomb, A.L., 2006. Enhancement of
transdermal delivery of 6-b-naltrexolviaacodruglinkedtohydroxybupropion.
Journal of Controlled Release 113, 137–145.
Kiptoo, P.K., Paudel, K.S., Hammell, D.C., Hamad, M.O., Crooks, P.A., Stinchcomb, A.L.,
2008. In vivo evaluation of a transdermal codrug of 6-b-naltrexol linked to