Introduction
Food, dietary supplements and their components can have impact on tlie achievement ol
dmg action and on the side effect profiles of various drugs. Upon entry into the stomach,
food may alter the rate or the extent of drug absorption through a variety of direct and
indirect mechanism. For certain drugs, lx)od may enhance the rate of absorption, while it
may reduce the rate of absolution of other drugs. The interactions are not always
detrimental to therapy, but in some cases can be used to improve dmg absorption or to
minimize adverse effects. These interactions have received more interest recently (Fuhi-,
1998), As new drug approvals occur there is less information available about their
adverse effects, interactions and about the use of herbal medicines and dietary
supplements. These products are not carefully monitored, and may contain little amount
of ingredient mentioned on the label. Some of the herbs used can interact adversely with
prescription drugs such as ephedra and feverfew. Ephedra is a stimulant that can cause
hypertensive crises in patients under monoamine oxidase inhibitors therapy. Feverfew
has anticoagulant properties that can enhance the effects of warfarin (Fleming, 1998;
Lippman and Nash, 1990). Increased acidic environment of stomach results in the
destruction o f acid-labile drugs, such as penicillin G, ampicillin and dicloxacillin
(Beverly et ai, 2003). In other cases, food components such as calcium or iron, may form
complexes with less easily absorbed dmgs like tetracycline, sodium fluoride and
ciprofloxacin (Shah et a/.,l999). In many cases, the actual mechanism by which food
interferes with absorption is not known, but interactions may occur through three
methods: reduced rate or extent of absorption, increased rate or extent o f absorption, or
through chemical/pharmacologic effects (Alonso and Varela, 2000).
The bioavailability of some drugs may be enhanced by food, for example, an acid
environment is necessary for the absorption of ketoconazole. The absorption of
griseofulvin is increased by high fat diet, Fenofibrate, mebendazole, isotretinoin,
tamsulosin, carbamazepirie and labetalol are some examples of drugs that show better
absorption while taken with food (Bennet and Brown, 2003; Sindhu et aL, 2004). There is
a common chemical or pharmacological interaction between alcohol and dmgs that have
sedative effects like opiates, benzodiazepines and antihistamines.The effect o f these
dmgs are usually potentiated by the consumption o f alcohol. Another alcohol-related
Chapter I _____________________________________________ Introduction
Ph. D Thesis 1 " Jam iaHamdard
interaction is tlie competitive inhibition o f the enzyme aldehyde dehydrogenase. Nausea,
vomiting, flushing, dizziness and tachycardia may occur with exposure to alcohol in
patients taking some cephalosporins, ketoconazole, metronidazole and sulfonylureas. In
addition, chronic alcohol overuse can increase the toxicity o f some drugs, as with
acetaminophen and methotrexate, or reduce the drugs efficacy, as with phenytoin (Lieber,
1994).
Components o f food may antagonize the desired effect o f the drug, as in the case o f
warfarin. Vitamin K containing foods reduce the effectiveness of warfarin. Changing to a
diet with increased consumption of leafy and/or dark green vegetables, such as spinach
and turnip greens, could decrease the degree of anticoagulation effect of warfarin due to
additional supply of vitamin K (Booth et ai, 1997). Perhaps the most feared food-drug
interaction is that between monoamine oxidase inhibitors (MAOIs) and tyi'amine, which
is found in a variety of aged, fermented, overripe or pickled foods and beverages and, to a
lesser extent, chocolate and yeast-containing foods. Tyramine is indirectly
sympathomimetic, when its metabolism is suppressed as by MAOIs, it can cause a
significant release o f norepinephrine, resulting in markedly increased blood pressure,
cardiac arrhythmias, hyperthermia and cerebral hemorrhage (Brown et al, 1989;
Livingston and Livingston, 1996). There are variety o f dmgs that show interaction with
flavonoids found in grapefruit juice that leads the inhibition of certain enzymes in the
cytochrome P450 system, which results in reduced metabolism of drugs that are cleared
by the same system (Bailey et al., 1998). Some examples of food and its components
affecting dmg absorption, disposition and their efl^ct as given as under:
(1) Antibiotics
® Cephalosporins, penicillin: Acid secreted by gut after food destroy these acid
labile daigs.
® Erythrom ycin: Fruit juice or wine consuption decrease the drug's effectiveness.
® Tetracycline: Dairy products reduce the drug's absorption and effectiveness.
(2) Anticonvulsants
® Dilantin, phenobarbital: Increase the risk of anemia and nerve problems due to
deficiency of folalte and other B vitamins.
chapter 1 ___________________________ Introduction
Ph. D Thesis 2 Jamia Hamdard
(3) Antidepressaiits
LithiMiii: A low-salt diet increases the risk o f lithium toxicity; excessive salt
reduces the drug's efficacy.
MAO inhibitorss Foods high in tyramine (aged cheese, processed meaits,
legumes, wine and beer among others) can produce a hyfiertensive crisis.
® Tricyclics: Many foods, especially legumes, meat, fish and foods high in Vitamin
C reduce absorption of the drugs,
(4) Antihypertensives and heart medications
® ACE inhibitors: Food lowers the absorption of the drugs.
® Alpha blockers: Liquid or food avoid excessive drop in blood pressure.
» A ntiarrhytlim ic drugs; Caffeine increases the risk of irregular heartbeat.
® Beta blockers; Food, especially meat, increases the drug's effects and can cause
dizziness and low blood pressure.
® Digitalis: Milk and high liber foods, which reduce absoiption, increases
potassium loss.
(5) Asthma drugs
® Pseudoephedrine: Caffeine increase feeling of anxiety and nervousness.
® Theophylline: High protein diet reduces absorption. Caffeine increases the risk o f
drug toxicity.
(6) Cholesterol lowering drugs
® Cholestyramine: Increases the excretion of folate and fat soluble vitamins.
® Gemfibrozil; Fatty foods decrease the drug's efficacy in lowering cholesterol,
(7) H eartburn and ulcer medications
“ Antacids: Interfere with the absorption of many minerals.
® CImetidine, famotidine, sucralfate: High protein foods, caffeine and other items
that increase stomach acidity.
(8) Hormone preparations
® O ral contraceptives: Salty foods increase fluid retention. Dmgs reduce the
absorption of folate, vitamin B6 and other nutrients.
® Thyroid drugs; Iodine-rich foods lower the dmg's efficacy.
Chapter I__________ ____________________________________________ Introduction
Ph. D Thesis 3 Jamia Hamdard
(9) Laxatives
‘s IVIiiiera! Oils; Overuse can cause a deficiency o f vitamins A, D, E, and K,
(10) Painkillers
a Aspirin and stronger nonsteroiclfi! asiti-iiiflamrnatory drugs: Food lowers the
risk of gastrointestinal irritation. Alcohol increases the risk o f bleeding.
(11) SleepiMg pills, tranquilizers
® Benzodiazepines; Caffeine increases an.x.iety and reduce drug's ettectiveness
(Sarah, 1998; Williams et al.. 1996; Anonymous, 2003; Walker e( al.. 1996).
According to the Code of Federal Regulations, bioavailability is the rate and extent
(fraction or the percentage of the dose) to which the active drug ingredient or therapeutic
moiety is absorbed from a dtxig product and becomes available at the site of drug action
(Lobenberg and Amidon, 2000). Oral bioavailability depends on a number of factors,
primarily drug penneabllity, aqueous solubility, dissolution rate, presystemic metabolism,
first-pass metabolism and susceptibility to efflux mechanisms. Among these l^ictors low
permeability and poor solubility stands as the most frequent causes o f low oral
bioavailability (Burnside et al., 2005).
Food and its components interact with co-adrninistered drugs and affect their availability
across intestine. Several pharmacokinetic parameters are used to judge the clinical
importance of fbod/dmg interachons. The concept that botanical supplements could
interact with conventional medications is understandable given that food-drug
interactions have been recognized ftir a variety of fruits, spices and vegetables that
constitute part of the nonnal human diet. Many food-drug interactions have
phytochemical-mediated pharmacokinetic components. For example, iuranocoumarins
present in grapefruit juice inhibit intestinal CYP3 A4 and have been shown to increase the
oral bioavailability of medications that are CYP3A4 substrates e.g., felodipine,
midazolam, cyclosporine. The human diet contains many different nutrients, several
compounds that are not nutrients, and additives. According to studies where effects of
carbohydrates, fat and proteins (macro-nutrients) were determined on drug absorption
and metabolism, changes in micro- and macro-nutrient composition of the diet can affect
absoiption and/or elimination of drugs (Welling, 1996). The effects of non-nutrients and
Chapter 1 _____________ ___________________________________
Ph. D Thesis 4 Jamia Hamdard
additives in food may also exert an et'fect on bioavailability of dmgs. Some drugs, which
normally are not interacting with food components, might interact during absoiption with
the components of plant material, causing unexpected drug effects, such as several times
higher or lower dmg concentrations in the circulation (Wallace and Amsden 2002).
Polyphenols (e.g. anthocyanins, couniarins, flavonoids, lignans and tannins), present in
herbs, vegetables, fmits, flowers, and leaves in many plants, are believed to be beneficial
to human health by exerting biological effects such as free radical scavenging.
Bioavailability of polyphenols has been studied in~vivo (Hollman et al., 1995; Miyazawa,
2000) and in-vitro (Kuo et a l, 1998, Murota et al., 2000, 2002). Most dietary flavonoids
present in food exist as 0-glycosides with glucose, glucorhamnose, galactose, arabinose,
or rhamnose (Heim et al., 2002). The f3-linkage of these glycosides resist hydrolysis
caused by acidity in the stomach and the attack by pancreatic enzymes, However, (3-
endoglucosidases present in small intestine are able to hydrolyse flavonoid glycosides
(Spencer et al., 1999). Additionally, colonic microflora hydrolyses the sugar moiety from
the flavonoid aglycone, thus increasing the absorption of flavonoids, During absorption,
the flavonoids may interact with metabolising enzymes and transport proteins, and thus
affect the uptake of co-administered drugs. Indeed, polyphenols are potent inhibitors or
inducers of CYPs, UGTs and transport proteins, if consumed in large amounts (Zhai et
al., 1998, Conseil et al,, 1998, Ohnishi cl al., 2000). Spices along with their components
may also effect drug absorption and metabolism.
Some natural compounds have demonstrated to increase the absorption and
bioavailability of co-administered drugs. Bioavailability and absoiption enhancement
through co-administration of drugs with natural compounds from plants are considered to
be very simple and comparatively safe. Bioavailability enhancing activity of natural
compounds from medicinal plants may mainly be attributed to various mechanisms such
as P-gp inhibition activity, non-specific mechanisms promoting rapid absorption o f drugs
such as increased blood supply to the gastrointestinal tract, decreased hydrochloric acid
secretion preventing breakdown of some drugs, non-specific mechanisms inhibiting
enzymes participating in metabolism of drugs. In many cases, bioavailability and
absorption-enhancing effect of natural compounds from medicinal plants were reported to
be attributed to inhibition of P-gp, Flavone, quercetin and genistein have showed a
Chapter I _______________________________________ Introduction
Ph. D Thesis 5 Jamia Hamdard
Chapter I Introduction
considerable P-gp inhibition activities. Additionally, naringin and sinomenine were also
reported to be inhibitors for efflux transporters such as P-gp and breast cancer resistance
protein (Tsai et a l, 2001; Chan et al., 2006). Attenuation of physical barrier such as an
increase in intestinal brush border membrane fluidity and inhibition o f metabolic
enzymes participating in biotransformation of drugs were reported to be absorption
enhancing mechanisms of natural compounds (Khajuria et al., 2002). Many absorption
enhancers are effective in improving the intestinal absorption, such as bile salts,
surfactants, fatty acids, chelating agents, salicylates and polymers as shown in Table 1.1
(Lundin et a l, 1990; Aungst et a l, 1991). Surfactants including bile, bile salts and fatty
acids act as absoiption enhancers by increasing the solubility of hydrophobic drugs in the
aqueous layer or by increasing the fluidity of the apical and basolateral membranes.
Calcium chelators such as EDTA i-educe the extracellular calcium concentration, leading
to the dismption of cell-cell contacts. Chitosan, particularly trimethylated chitosan, was
reported to increase dmg absorption via paracellular route by redistribution o f the
cytoskeletal F-actin, causing the opening of the tight junctions (Schipper et al., 1997).
Table 1.1 List of compounds shown to have intestinal absorption eiiliaiidiig effects
Category Compounds
Bile salts Sodium cholate, sodium deoxycholate
NoEi“ioEic surfactants Polyoxyethylene alkyl ethers, polysorbates
Ionic surfactants Sodium lauryl sulfate.
Dioctyl sodium sulfosuccinate
Fatty adds Sodium caprate, oleic acid, glycerides, natural oils,
medium-chain glycerides, phospholipids,
polyoxyethylene glyceryl esters,
acyl carnitines and cholines,
palmitoyl carnitine, lauroyl choline
Salicylates Sodium salicylate, sodium methoxysalicylate
Chelating agents EGTA, EDTA
Swellable polymers Starch, polycarbophil, chitosan
Others Citric acid
Ph. D Thesis ^ Jarnia Hamclard
Phytocoiistitueiits as bioenharicers
Quercetln
Quercetin is a flavonoid found in citrus I'ruits, It is reported that this flavanoid increase
bioavailabihty, blood levels and efficacy of a number o f drugs such as diltiazem (Choi
and Li, 2005), digoxin (Wang et a!., 2004) and epigallocatechin gallate (Anup et a/.,
2005), The absorption of epigallocatechin gallate has been enhanced with red onion
supplementation, which is a rich source of quercetin. The AUC of epigallocatechin
gallate determined over a period of 6 h increased from 1323 to 1814 ng.h/ml, when co
administered with quercetin.
Genlstetn
Genistein, well known as a phytoestrogen (Kurzer and Xu, 2003) inhibits P-gp, BCRP
and MRP2 efflux function. The intestinal absorption of paclitaxel, a substrate for efflux
transports such as P~gp, BCRP and MRP2 considerably increased when co-administered
with genistein. It has been reported that the inhibition of the efflux transporters by
genistein improve systemic exposure of paclitaxel (Li and Choi, 2007),
Nariiigin
Naringin is the major flavonoid glycoside found in grapefruits, that shows the inhibition
of P“gp and CYP3A in rats (Zhang el a!., 2000). AUC of paclitaxel is increased
significantly in presence of naringin (49,1% for naringin at 10 mg/kg) (Lim and Choi,
2006).
Sinomenine
Paeoniflorin, bioactive monoterpene glucoside has a poor bioavailability (3-4%) when
administered orally (Takeda et aL, 1995). Co-administration o f paeoniflorin with
sinomenine, an alkaloid extracted from Sinomenium acutim, significantly altered the
pharmacokinetic behaviors of paeoniflorin in rats (Liu et ciL, 2005). The results of AUC
obtained in the study demonstrated that oral bioavailability of paeoniflorin was enhanced
by more than 12 times in rats treated with sinomenine.
Piperine
Piperine is a major alkaloidal component of Piper nigrum Linn. Piperine, or mixtures
containing piperine, has been shown to increase the bioavailability, blood levels and
efficacy of a number of drugs including vasicine, sparteine, sulfadiazine, rifampicin,
Chapter I_______________________________________________ ___________
Ph, D Thesis 7 Jamia Hamdard
phenytoin and propranolol (Atal el al„ 1981; Bano et al„ 1987; 1991).
Glycyrrliizin
Glycyrrhizin is a, triterpenoid saponin Ibund in Glycyrrhiza glabra Linn, Glycyrrliizin
showed a more potent absorption enhancing activity than caproic acid at the same
concentration tested (Liiai et al., 2005). The absorption-enhancing activity of sodium
deoxycholate and dipotassium-glycyrrhizinate was much greater when coadministered
with glycyrrhizin. The absoiption enhancing activity of glycyrrhizin was increased by
presence of other absoiption enhancers (Sakai et al., 1999; Imai et al., 2005).
Nitrile glycosides
Nitrile glycosides and its derivatives are components derived from the pods of Moringa
oleifera Lam. These glycosides enhanced the absorption of commonly used antibiotics
such as rifampicin, tetracycline and ampicillin, vitamins and nutrients (Khanuja et al.,
2005).
CiMtiin oil
Cuminum cyminum Linn, is an annual herb, its fruits are generally used as spice.
Bioavailability enhancing activity of C. cyminum was revealed toward a number o f drugs
(Qazi et al., 2009). Various volatile oils and luteolin and other flavonoids seemed to
attribute the bioavailability/bioefficacy enhancing activity. Especially luteolin has
demonstrated to be a potent P-gp inhibitor in the literature (Boumendjel et a l, 2002).
Pepperinliit oil
Peppermint oil extracted from mentha species increased cyclosporine maximum
concentration (C„,aO and area under the concentration versus time curve (AUCo-a) from
0.60 to 1.6 fig/ml and 8.3 to 24.3 ng.h/ml respectively (Wacher et a/.,2002).
Chapter I _____________________________________________________ Introduction
Ph. D Thesis 8 Jamia Hamdard
References
Alonso, A.E., and Varela, M.G. (2000). Drugs-nutrient interactions: a potential problem
during adolescence. European Journal o f Clinical Nutrition, 54, 69-74.
Anonymous, (2003). British National Formulary, 46 '̂' Ed., British medical association
and Royal Pharmaceutical Society, London, pp.67-75.
Anup, K., Sonia, G., Swati, K., Shrirang, N., Waheed, R., Vadim, I., Aleksandra, N.,
Matthias, R. (2005). The studies on bioenhancer effect of red onions and other
nutrients on the absorption of epigallocatechin gallate from green tea extract in
human volunteers, 2nd International Conference on Tumor Progression and
Therapeutic Resistance Proceedings held at Boston, pp.89.
Atal, C.K., Zutshi, U., Rao, P.O. (1981), Scientific evidence on the role of Ayurvedic
herbals on bioavailability of drugs. Journal o f Ethnopharmacology, 4, 229-232.
Aungst, B..I., Blake, .I.A., Hussain, M.A, (1991). An in-vitro evaluation of metabolism
and poor membrane permeation impeding intestinal absorption of leucine enkephalin,
and methods to increase absorption. Journal Pharmacology Experimental
Therapeutics, 259, 139-145.
Bailey, D.G,, Malcom, ,f., Arnold, A., Spence, J.D. (1998). Grapefruit juice-drug
interactions. British Journal o f Clinical Pharmacology, 46, 101-110.
Bano, G., Amla, V., Raina, R.K., Zutshi, U., Chopra, C.L. (1987). The effect of piperine
on phannacokinetics of phenytoin in healthy volunteers. Planta Medica, S3, 568-569.
Bano, G., Raina, R.K., Zutshi, U., Bedi, K.L., Johri, R.K., Shanna, S.C. (1991). Effect
of piperine on bioavailability and pharmacokinetics of propranolol and theophylline
in healthy volunteers. European Journal o f Clinical Pharmacology, 41, 615-617.
Bennet, P.N., Brown, M..1. (2003). Clinical Pharmacology, 9̂ '‘ Ed., Churchill
Livingstone publishers, New York, pp.128-133.
Beverly, J.M., Eric, H.F., Jonathan, .T.W. (2003). Handbook o f food-drug interactions,
CRC Press, Boca Raton, London, New York, Washington, D.C. pp.27-29.
Booth, S.L., Charaley, J.M., Sadowski, J.A., Saltzman, E., Bovill, E.G., Cushman, M.
(1997). Dietary vitamin K1 and stability of oral anticoagulation: proposal of a diet
with constant vitamin Kl content. Thrombosis and Haemostasis, 77(3), 503-509.
Chapter 1_________________________________________________________ Introduction
Ph. D Thesis 9 Jamia Hamdard
Boumencljel, A., Di-Pietro, A., Dumontet, C., Barron, D. (2002). Recent advances in the
discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein
responsible for cancer cell multidrug resistance. Medical Research Review, 22, 512-
529.
Brown, C., Taniguchi, G., Yip, K. (1989), The monoamine oxidase inhibitor-tyramine
interaction. Journal o f Clinical Pharmacology, 29, 529-232.
Burnside, B., Chang, R.K., Shojaei, A, (2005). Phamiaceutical compositions including
ACE/NEP inhibitors and bioavailability enhancers, United State Patent, 6890918.
Chan, K., Liu, Z.Q., .Hang, Z.H., Zhou, H., Wong, Y.F., Xu, H.X., Liu, L. (2006). The
effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut
sac model. Journal o f Etlmopharmacology, 20, 425-432,
Choi, J.S., Li, X. (2005). Enhanced diltiazem bioavailability after oral administration o f
diltiazem with quercetin to rabbits. International Journal o f Pharmaceutics, 297, 1-8.
Conseil, G., Baubichon, C.H., Dayan, G., Jault, J.M., Barron, D., Di Pietro, A. (1998).
Flavonoids; a class of modulators with bifunctional interactions at vivinal ATP- and
steroid binding sites on mouse P~glycoprotein. Proceeding o f National Academy o f
Science, 95, 9831-9836.
Fleming, T. (1998), Ephedra sinica, hi PDR fo r Herbal M e d i c i n e s . Ed., Montvale,
NJ: Medical Economics Company Inc, pp.75-77.
Fuhr, U. (1998). Drug interactions with grapefruit juice; extent, probable mechanism
and clinical relevance. Drug Safety, 18, 251-272.
Heim, K.E., Tagliaferro, A.R., Bobilya, D.,f. (2002). Flavonoid anitoxidants: chemistry,
metabolism and stmcture-activity relationships. Journal Nutritional Biochemistry, 13,
572-584.
Hollman, P.C.H,, De Vries, .T.H.M., Van Leeuwen, S.D., Mengelers, M..I.B., Katan,
M,B, (1995). Absorption of dieatary quercetin glycosides and quercetin in healty
ilostomy volunteers. American Journal o f Cliniccd Nutrition, 62, 1276-1282.
Imai, T., Sakai, M,, Ohtake, H,, Azuma, H., Otagiri, M. (2005). Absoiption enhancing
effect of glycyrrhizin induced in the presence o f capric acid. International Journal o f
Pharmaceutics, 27, 11-21.
Chapter I ______ _______________________________________________Introduction
Ph. D Thesis 10 Jamia Hamclard
Khajuria, A., Thusu, N„ Zutshi, U. (2002), Piperiiie modulates permeability
characteristics o f intestine by inducing alterations in membrane dynamics: influence
on brush border membrane tluidity, ultrastaicture and enzyine Idnetics.
Phytomedicine. 9, 224-231.
Khanuja, S.P.S., Arya, J.S., Tiruppadiripuliyur, R.S.K., Sailcia, D., Kaur, H., Singh, M.
(2005). Nitrile glycoside useful as a bioenhancer o f drugs and rmtrients, process ot its
isolation h'QmMoringa oleifem. United States Patent 6858588,
Kuo, S,M. (1998). Transepithelial transport and accumulation of flavone in human
intestinal Caco-2 cells. Life Sciences, 63, 2323-2331.
Kurzer, M., Xu, X. (2003). Dietary phytoestrogens. Annual Review o f Nutrition, 17,
353-381.
Li, X., Choi, J.S. (2007). Effect of genistein on the pharmacokinetics o f paclitaxel
administered orally or intravenously in rats. International Journal o f Pharmaceutics,
337, 188-193,
Lieber, C.S. (1994). Mechanisms of ethanol-drug nutrition interactions. Journal o f
Toxicology Clinical Toxicology, 32, 631-681.
Lim, S.C., Choi, J.S. (2006), ElTects of naringin on the pharmacokinetics of intravenous
paclitaxel in rats. Biopharmaceutics and Drug Disposition. 27, 443-447.
Lippman, S.B., Nash, K. (1990). Monoamine oxidase inhibitor update: potential adverse
food and drug interactions. Drug Safety, 5, 195-204.
Liu, Z.Q., Zhou, H., Liu, L„ Jiang, Z.H., Wong, Y.F., Xie, Y., Cai, X., Xu, H.X., Chan,
K. (2005). Influence of co-administrated sinomenine on pharmacokinetic fate of
paeoniflorin in unrestrained conscious rats. Journal o f Ethnopharmacology, 13, 61-
67.
Livingston, M.G., Livingston, H.M. (1996). Monoamine oxidase inhibitors: an update
on drug interactions. Drug Safely, 14, 219-227.
Lobenberg, R., Amidon, G.L. (2000). Modem bioavailability, bioequivalence and
biopharmaceutics classification system: new scientific approaches to international
regulatory standards. European Journal o f Pharmaceutics and Biopharmaceutics, 50,
3-12.
Chapter I __________________________________________ Introduction
Ph. D Thesis II JamiaHam dard
LAindin, S., Artursson, P. (1990). Absorption of vasopressin analogue, cleamino-8-D-
arginine-vasopressin (DAVP), in a human intestinal epithelial cell line, CaCO-2.
InterncUionalJournal o f Pharmaceutics, 64, 181-186,
Miyazawa, T. (2000). Absorption, metabolism and antioxidative elTects of tea catechin
in humans. Biofactors, 13, 55-59.
Murota, K., Shimizu, S., Chujo, H,, Moon, J-H., Terao, ,1. (2000). Efficiency of
absorption and metabolic conversion of quercetin and its glycosides in human
intestinal cell line Caco-2. Archives o f Biochemistry and Biophysics, 384, 391-397.
Murota, K., Shimizu, S., Miyamoto, S., Izumi, T., Obata, A., Kikuchi, M., Terao, .1.
(2002), Unique uptake and transport of isoflavone aglycones by human intestinal
Caco-2 cells: comparison of isoflavonoids and flavonoids. 1956-1961.
Ohnishi, A., Matsuo, H., Yamada, S., Takanaga, H„ Morimoto, S., Shoyama, Y.,
Ohtani, H., Sawada, Y. (2000), Effect of furanocoumarin derivatives in grapefruit
juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome
P450 3A4. Brazilian Journal o f Pharmacology, 130, 1369-1377.
Qazi, G.N,, Bedi, K.L,, Johri, R., Tikoo, M,K., Tikoo, A.K., Shamia, S.C., Abdullah,
S.T., Suri, 0,P,, Gupta, B.D., Suri, K.A., Satti, N,K., Khajuria, R,K., Singh, S.,
Khajuria, A,, Kapahi, B,K. (2009), Bioavailability/bioefficacy enhancing activity of
Cutnimm cyminum. and extracts and fractions thereof. United States Patent 7514105.
Sakai, M., hnai, T., Ohtake, H,, Azuma, H„ Otagiri, M, (1999). Simultaneous use of
sodium deoxycholate and dipotassium glycyrrhizinate enhances the cellular transport
of poorly absorbed compounds across Caco-2 cell monolayers. Journal o f Pharmacy
and Pharmacology, 51, 27-33.
Sarah, E.B, (1998). Pharmacotherapy perspectives, dmg-food interactions. Journal o f
the Pharmacy Society o f Wisconsin, 28-35,
Schipper, N.G.M., Olsson, S., Hoogstraate, J.A., Deboer, A.G., Vamm, K.M.,
Artursson, P. (1997). Chitosans as absorption enhancers for poorly absorbable drugs-
2, mechanism of absoiption enhancement. Pharmaceutical Research, 14, 923-929,
Shah, A., Liu, M,C., Vaughan, D, Heller, A.H. (1999), Oral bioequivalence o f three
ciprofloxacin formulations Ibllowing single-dose administration: 500 mg tablet
compared with 500 mg/10 mL or 500 mg/5 mL suspension and the effect o f food on
Chapter I_____ ___________________________________ ____ ____________ Introductim_
Ph. D Thesis 12 Jarnia Hamdard
the absorption of ciprofloxacin oral suspension. Journal o f Antimicrobial
Chemotherapy, 43, 49-54.
Sindhu, S., Malhotra, S., Garg, S.K. (2004). Influence of high fat diet (butter) on
pharniacolcinetics of phenytoin and carbamazepine. Methods and Findings in
Experimental Clinical Pharmacology, 26(8), 634-638.
Spencer, J.P.E., Chowrimootoo, G., Chouldhuiy, R., Debnam, E.S., Srai, S.K., Rice-
Evans, C. (1999). The small intestine can both absorb and glucuronidate luminal
flavonoids. FEES Letters, 458, 224-230.
Takeda, S., Isono, T., Wakui, Y., Matsuzaki, Y., Sasaki, H., Amagaya, S., Maruno, M.
(1995), Absorption and excretion of paeonillorin in rats. Journal o f Pharmacy and
Pharmacology, 41, 1036-1040.
Tsai, T.H., Lee, C.H., Yeh, P.H. (2001). Effect of P-glycoprotein modulators on the
pharmacokinetics of campothecin using microdialysis. British Journal o f
Pharmacology, 134, 1245-1252.
Wacher, V.J., Wong, S., Wong, H.T. (2002). Peppermint oil enhances cyclosporine oral
bioavailability in rats: comparison with D-alpha-tocopheryl poly (ethylene glycol
1000) succinate (TPGS) and ketoconazole. Journal o f Pharmaceutical Science, 91(1),
77-90.
Walker, S.E., Shulraan, K.I., Tailor, S.A.N., Gardner, D. (1996). Tyiumine content o f
previously restricted foods in monoamine oxidase inhibitor diets. Journcd o f Clinical
Psychopharmacology, 16, 383-388.
Wallace, A., Amsden, G. (2002). Is it really OK to take this with food? Old interactions
with a new twist. Journal o f Clinical Pharmacology, 42, 435-441.
Wang, Y.H., Chao, P.D., Hsiu, S.L., Wen, K.C., Hou, Y.C. (2004). Lethal quercetin-
digoxin interaction in pigs. Life Sciences, 74, 1191-1197.
Welling, P.G. (1996). Effect of food on dmg absorption. 16, 383-415.
Williams, L., Hill, D.P., Davis, .I.A., Lowenthal, D.T. (1996). The influence o f food on
the absorption and metabolism of dings: an update. European Journal o f Drug
Metabolism, and Pharmacokinetics, 21, 201-211.
Chapter 1 ________ ____________________________________ Introduction
Ph. D Thesis 13 Jamia Hamdard
Zhai, S., Dai, R,, Friedman, F.K., Vestal, R.E. (1998). Comparative inhibition of human
cytochromes P450 lA l and 1A2 by flavonoids. Drug Metabolism and Disposition,
26, 989-992.
Zhang, H., Wong, C.W., Coville, P.F., Wanwimolruk, S. (2000). Effect o f the grapefrait
flavonoid naringin on pharmacokinetics of quinine in rats. Drug Metabolism and
Drug Interaction, 17, 351-363,
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