Bioavailability Enhancement by Piperine: A Review

Shailendra Wadhwa*,1, Sarita Singhal2, Swati Rawat3

1Research Scholar, MJRP University, Jaipur (Raj).
2Department of Pharmacy, MJRP University, Jaipur (Raj).
3SND College of Pharmacy, Yeola, Nashik, (Maharashtra).

Abstract
Oral absorption of drug is very important issue especially when the drug is
poorly bioavailable, given for long periods and expensive. Poorly
bioavailable drugs remain sub-therapeutic because a major portion of a
dose never reaches the plasma or exerts its pharmacological effect unless
and until very large doses are given which may also lead to serious side
Received on: 30/08/2014
Accepted on: 30/09/2014 effects. Any significant improvement in bioavailability will result in
Published on: 15/10/2014 lowering the dose or the dose frequency of that particular drug. Several
approaches have been used to maximize oral bioavailability, but with the
Corresponding Author discovery of the first bioavailability enhancer piperine in 1979, a new class
Shailendra Wadhwa, of drug and a new concept was introduced in to the science. Bioenhancers
Research Scholar, MJRP University, or bioavailability enhancers are mostly the plant based molecules which
Jaipur (Raj promote the biological activity or bioavailability or the uptake of drugs in
Email: [email protected]
combination therapy. This review article concludes the bioavailability
enhancing property of piperine.
Keywords: Piperine, bioenhancer, bioavailability, Piper nigrum,
combination therapy.

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DOI: 10.15272/ajbps.v4i36.576

Cite this article as:

Shailendra Wadhwa, Sarita Singhal, Swati Rawat. Bioavailability Enhancement by Piperine: A Review. Asian Journal of Biomedical
and Pharmaceutical Sciences; 04 (36); 2014,1-8.
 Shailendra Wadhwa et al: Asian Journal of Biomedical and Pharmaceutical Sciences; 4(36) 2014, 1-8.

INTRODUCTION
Drug discovery is no longer a game of chance or just C.K. Atal, the Director of the institute scrutinized a list
limited to the availability of new technology. Better of ancient Indian Ayurvedic formulations used in the
understanding of various approaches and key learning treatment of a wide range of diseases. He found that
from the past with the appropriate strategy for the one of the groups of herbals which has been
future is essential to make a significant difference.[1] documented very frequently as essential part of about
During the past few years a large number of approved 70% of Ayurvedic prescriptions, is `Trikatu`, that
new drug applications have originated from the comprises three acrids viz. long pepper, black pepper
biotechnology industry and analysts expect a and dry ginger in equal proportions. He observed that a
continuation of pharmaceutical-biotechnology alliances majority of Ayurvedic formulations contained either
to help expand pipelines.[2] Similarly, natural products Trikatu or else one of the ingredients of Trikatu,
have contributed nearly half of all small molecules namely Piper longum (210 formulations out of 370
approved in this decade. It has been suggested that the reviewed) used in a large variety of diseases. In
current drug discovery approach of finding new entity subsequent experiments using various drugs and
drugs, if shifted to combining existing agents may be extracts with trikatu and its ingredients they found that
helpful. Therefore natural product drug discovery mainly piperine enhances the bioavailability of most of
based on ethnopharmacology and traditional the drugs used in experiments and the role of ginger is
medicines may also be considered as attractive to regulate intestinal function to facilitate
strategic options.[3,4] absorption.[11,12,13]
Recently the combination of therapeutic agents with ISOLATION AND EXTRACTION OF PIPERINE FROM
natural compounds possessing absorption improving PIPER SPECIES
activities has gain great interest for enhancing the Piperine was discovered by Hans Christian rsted in
bioavailability of poorly bioavailable drug. Natural 1819. It is known as one of the main components of
compounds such as piperine, quercetin, sinomenine, pepper. [14] Piperine is responsible for the pungency of
glycyrrhizin, gentistein, naringin, niazeridine and black pepper and long pepper, along with chavicine (an
lysergols were evaluated for their bioenhancing effect, isomer of piperine). [15] It can be isolated from the fruits
along with modern medicines.[5] of P. nigrum or P. longum. The powdered fruits of the
Plants have been the source of medicines since plant are extracted with dichloromethane at room
thousands of years. Members of the botanical family temperature with stirring for 12 hours. The extract is
piperaceae were among the first cultivated plant and filtered, concentrated in vacuum, and then the residue
the species of the genus Piper are the important is purified on an alumina column. Pure piperine can
medicinal plants used in various systems of medicine.[6] also be obtained by crystallization from ethanol, which
Black pepper (Piper nigrum) and long pepper (Piper may be required for food and/or medicinal usages.
longum) are the best known spices in the family and Piperine is obtained directly from the crude residue in
are probably among the most recognized spices in the lesser amounts by extraction in alcohol, filtration and
world. Both the peppers have been used medicinally successive crystallization. Piperine can be synthesized
for centuries. Black pepper alone accounts for about from the interaction of piperyl chloride (formed from
35% of the worlds total spice trade.[7,8] piperic acid and phosphorus pentachloride) and
Generally the fruits of P nigrum and P longum contain piperidine. [16]
1.02.5% volatile oil, 59% alkaloids, of which the PROPERTIES OF PIPERINE
major ones are piperine, chavicine, piperidine, and PHYSICAL AND CHEMICAL PROPERTIES OF
piperetine. Most of the pharmacological properties of P PIPERINE
nigrum and P longum fruits are attributed to a Piperine is a nitrogenous pungent substance.[17] The
piperidine alkaloid; piperine which is present in the chemical structure of piperine places it in the group of
fruits in amounts of 1.77.4%.[9] cinnamamides.[18] The congeners of cinnamamides
HISTROY AS BIOENHANCER possess sedative, hypnotic, anticonvulsant,
The term bioavailability enhancer or bioenhancer was antidepressant, and skeletal muscle relaxing
first coined by Indian scientists C.K. Atal, the Director of properties. Highly pure piperine is needle-shaped or
the Regional Research laboratory, Jammu, who short rod-shaped light yellow or white crystalline
discovered and scientifically validated Piperine as the powder. It yields salts only with strong acids. The
worlds first bioavailability enhancer in 1979. solution of piperine in alcohol has a pepper-like taste.
Bioenhancers are molecules, which do not possess drug [19]

activity of their own at the dose used but promote and

augment the biological activity or bioavailability or the
uptake of drugs in combination therapy.[10]

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S IUPAC Name 1-[5-(1,3-Benzodioxol-5yl)-1-oxo-2,4- BIOENHANCING PROPERTY OF PIPERINE

No pentadienyl]piperidine BIOENHANCING DOSE OF PIPERINE
1 Chemical name 1- piperoyl piperidine
The effective bioenhancing dose of piperine for drugs
2 Molecular C17H19NO3
formula varies but lots of studies indicate that a dose of
3 Molecular mass 285.34 gm mol-1 approximately 10% (wt/wt) of the active drug or a
4 Percentage C= 71.55%, H=6.71%, N=4.91% and daily dose of at least 15-20 mg/day could be regarded
composition O=16.82% as an appropriate bioenhancing dose for most drugs.
5 Taste Tasteless at first, but burning aftertaste
This bioenhancing dose of piperine corresponds to
6 Melting point: 130oC
7 Density 1.193 gm cm-3 form several thousands to up to 40,000 times less than
8 pK (18) 12.22 the LD50 dose of piperine, as established in various
9 Solubility Insoluble in water, soluble in benzene experiments on rodents.[10, 29, 30].
and acetic acid ADVANTAGES OF USING PIPERINE AS
10 Stereoisomer isopiperine, isochavicine and chavicine BIOENHANCER
11 UV absorption 332 nm
maxima
There are various advantages of using bioenhancer in
(methanol) combination therapy. These are follows
Table 1: Properties of Piperine[20,21,22,23] Efficacy of drug is increase due to increase in
bioavailability.
Combination of bioenhancer with drug reduces the
dosage and dangers of drug resistance can be
minimized.
Adverse drug reaction/side effect and toxicity of
drug will be minimized because of reduced dosage.
This is especially true of anticancer drugs like
Taxol.
Figure 1: Chemical structure of Piperine[24]
There are ecological benefits too eg. Toxol used to
PHARMACOKINETICS OF PIPERINE IN RAT treat ovarian cancer or breast cancer is derived
Piperine is rapidly absorbed through the GIT and could from bark of Pacific yew tree, one of the slowest
be detected in plasma as early as 15 min after growing trees in the world. At present to treat one
administration to rat.[25] 97% of piperine was absorbed patient, six trees, 25-100 years old need to be felled
after oral administration of piperine at a dose of 170 with bioenhancers fewer trees will be destroyed.
mg/kg to the male albino rats. 3% of the administered They can reduce inter-individual variability as well
dose was excreted up to 4 days as piperine in the feces as intra-individual variability as they increase the
and it is not detectable in urine. Piperine did not go bioavailability of drug.[30]
undergo any metabolic change during absorption from PROPOSED MECHANISM FOR BIOENHANCING
intestine but letter it is metabolized rapidly by liver EFFECT
and other tissue and maximum plasma concentration By action on drug metabolizing enzyme
was attained at about 6 hr. Urine is the major excretion One of the reasons for bioenhancing effect of piperine
route for piperine metabolites in rats as no metabolite is attributed to the interaction of piperine with
could be detected in faces. Half life (t1/2) was found to enzymes that participate in drug metabolism, such as
be 18.24 hr.[26] About 36% of the orally administered mixed function oxidases found in the liver and
piperine was excreted as conjugated phenols in urine intestinal cells or may be due to inhibition of hepatic
and 62% as methylenedioxyphenyl metabolites.[27] 4 and non hepatic drug metabolizing enzymes.
metabolites of piperine, viz. piperonylic acid, piperonyl Piperine may also interact with the process of oxidative
alcohol, piperonal and vanillic acid were identified in phosphorylation, or the process of
the free form in 0-96 h urine whereas only piperic acid activation/deactivation of certain metabolic pathways,
was detected in 0-6 h bile. Metabolism of piperine thus slowing down the metabolism and biodegradation
would involve an amidase which splits piperine at the - of drugs. This action of piperine results in higher
-CO--N-- bond followed by the oxidation of the side plasma levels of drugs, rendering them more
chain and scission of the methylene-dioxy group.[28] available for pharmacological action.
TOXICITY Glucuronyl transferase activity also inhibited by
The LD50 of piperine in mice and rats were found to be piperine through the lowering of the endogenous UDP
330 mg Kg-1 and 514 mg Kg-1, respectively. In sub acute glucuronic acid contents and decreased transferase
toxicity studies, piperine at the dose rate of 100 mg Kg-1 activity. Furthermore the aryl hydrocarbon
for 7 days was reported to be non toxic.[29] hydroxylase (AHH) and 7-ethoxycoumarin deethylase
(7 ECDE)) activities inhibited by piperine both under in

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vitro and in vivo conditions. Researcher showed that pathogen is increased or by enhancing the binding of
Methylenedioxyphenyl ring in piperine has been found drug to receptors like DNA or protein of the
to be responsible for inhibition of drug metabolizing pathogen.[30]
enzymes and piperine mediated inhibition of AHH BIOAVAILABILITY ENHANCEMENT BY PIPERINE
activity. [31,32] Pattanaik S, et al., (2009) evaluated the effect of
Piperine can reduce the biotransformation in gut by piperine (20 mg p.o.) on the pharmacokinetics of
inhibiting CYP3A activity in gut epithelial cells. carbamazepine (300 or 500 mg bid) in epilepsy
Inhibition of CYP3A by piperine in gut epithelial cells patients. The comparison of pharmacokinetic
will lead to total increase in drug bioavailability in parameters from blood samples at regular interval,
serum. Fewer drug molecules will be metabolized by after the administration of carbamazepine and
phase I enzymes in the gut and will not be available for carbamazepine along with piperine showed that
the phase II conjugation enzymes. This will lead to piperine significantly increased the mean plasma
increased concentration of untransformed drug concentrations of carbamazepine in both dose groups.
passing from gut in to blood and on to other tissue in There was a significant increase in AUC, average C(ss)
the body. Piperine may reduce CYP3A drug and a decrease in K(el) in both the dose groups. Cmax
biotransformation by acting as an inhibitor of CYP3A and tmax were increased significantly following piperine
activity.[33] administration in the 500 mg dose group. They
Piperine is a potent inhibitor of UDP-GDH and it exerts concluded that piperine could significantly enhance the
stronger effects on intestinal glucuronidation than in oral bioavailability of carbamazepine, possibly by
rat liver.[34] decreasing the elimination and/or by increasing its
By affecting blood supply to GIT and membrane absorption.[38]
fluidity Jin MJ, et al., (2010), investigated the enhanced oral
The mechanism of enhancing the drug bioavailability exposure of fexofenadine (10 mg/kg) in rats in the
can be explained by following possible explanations: a) presence and absence of piperine (10 or 20 mg/kg,
increased blood supply to the gastrointestinal tract, b) given orally). Results of study indicated that
effect on membrane fluidity with concentration combination of piperine increases the oral exposure
dependency. (AUC) of fexofenadine by 180% to 190% and
Piperine interacts with proteins embedded in the cell bioavailability approximately by 2-folds. They
membrane by stimulating leucine amino peptidase and concluded that this effect of piperine likely due to the
glycyl-glycine dipeptidase activity. This suggests that inhibition of P-glycoprotein-mediated cellular efflux
piperine could modulate the cell membrane dynamics during the intestinal absorption.[39]
related to passive transport mechanism due to its Janakiraman K, et al., (2011) aimed to include Piperine
apolar nature by interacting with surrounding lipids (bioenhancer) as a formulation additive in oral
and hydrophobic domain of cellular proteins. The formulations of Ampicillin Trihydrate. Physical mixture
improved bio availability of nutrients by the piperine is of Ampicillin Trihydrate and Piperine (1:1) was tested
perhaps due to its thermo nutrient action or for their compatibility and stability study. The above
thermogenic action. Bioavailability enhancing action of studies proved that Piperine can be used as a
drugs is partly due to enhancement of blood supply in formulation additive for bioenhancing effect in oral
enteric vessels as a result of local vasodilatation.[35,36] formulations of Ampicillin Trihydrate.[40]
By enhancing drug transport Shoba G, et al., (1998) studied the effect of piperine on
A resent work concluded in Regional Research the bioavailability of curcumin in rats and healthy
Laboratory, Jammu has shown that piperine acts as human volunteers at a dose 20 mg/kg and 20 mg and 2
modulator of cell membrane dynamics and help the g/kg to rats and 2 g respectively. Concomitant
transport of drugs across these barriers. Piperine form administration of piperine increases the tmax while
complex with drugs and help them reach the target site elimination half life and clearance significantly
rather than spread out non specifically. It may act as decreased and the bioavailability was increased by
an apolar molecule and form apolar complex with 154%. On the other hand in humans the increase in
drugs and solutes. It may modulate membrane bioavailability was 2000%. The study shows that
dynamics due to its easy partitioning thus helping in piperine enhances the serum concentration, extent of
efficient permeability of drugs across the barriers.[37] absorption and bioavailability of curcumin in both rats
Piperine may inhibit the capability of pathogen to and humans with no adverse effects.[41]
reject the drug. It is very useful in case of antibiotic Kasibhatta R, et al., (2007) conducted a crossover,
resistant strain of pathogen. Piperine may increase the placebo-controlled pilot study in eight healthy adult
entry of drug to pathogen either by modulating the males. Blood samples were collected from 1 to 144
signaling process so that accessibility of drug to hours post-dose of the subjects received piperine 20mg

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or placebo each morning for 6 days, and on day 7, double-blind, crossover study design. The results
nevirapine 200mg plus piperine 20mg or nevirapine indicate that supplementation with beta-carotene plus
plus placebo in a crossover fashion. Analysis of piperine for 14-days produced a 60% greater increase
pharmacokinetic data showed there was increase in in area under the serum beta-carotene curve (AUC) as
mean maximum plasma concentration (Cmax), area compared to beta-carotene plus placebo. They suggest
under the plasma concentration-time curve. The last that the improved serum response is non-specific and
measurable concentration (C(last)) [AUC(t)], AUC due to thermogenic property(s) of piperine.[46]
extrapolated to infinity (AUC(infinity)) and C(last) Supriya Veda, et al., (2009) found significantly
values of nevirapine was increased by approximately enhanced intestinal uptake of -carotene as a result of
120%, 167%, 170% and 146%, respectively.[42] consumption of pungent spices black pepper, red
Singh A, et al., (2010) found an increase of 57% and pepper, ginger, piperine and capsaicin. Study showed
88.53% in peak plasma levels and AUC respectively of higher in vitro absorption of -carotene in all spice-fed
metronidazole when given with piperine to male New animals. Dietary piperine, ginger, capsaicin and black
Zealand white rabbits (2.0-2.5 kg body weight).Three and red pepper increased the uptake of -carotene by
groups of rabbits were formed from which one group 147%, 98%, 50% and 59% and 27% respectively.
was considered as control and received only vehicle Results suggested that specific dietary spices may alter
(distilled water) orally. Remaining two groups were the ultra structure and permeability characteristics of
treated with metronidazole (20 mg/ kg) and intestines and which could form a food based strategy
combination of metronidazole (20 mg/ kg) and to possibly reduce vitamin A deficiency.[47]
piperine (10 mg/kg) respectively.[43] Boddupalli B M, et al., formulated gastroretentive
Pooja S, et al., (2007) evaluated the analgesic activity of microspheres of omeprazole along with piperine and
Piper nigrum (10 mg/kg) extract and its interaction estimated the pharmacokinetics parameters in rabbits.
with diclofenac sodium (5 mg/kg) and pentazocine (5 They found hat there was a significant increase in the
mg/kg) in albino mice (25-30 grams). Peripheral area under curve from 3.4411.093 mgh/mL to
analgesic activity was evaluated by acetic acid induced 14.4220.708 mgh/mL along with an increase in
writhing test, using diclofenac sodium, Piper nigrum Cmax. This clearly shows the increased absorption and
extract and their combination orally. Similarly central decreased metabolism of omeprazole when
analgesic activity was studied by tail flick method using administered along with piperine.[48]
pentazocine and Piper nigrum extract and their Desai SK, et al., (2008) evaluated the dose dependent
combination orally. Results showed significant potentiation of hepatoprotective activity of
decrease in writhes 78.43% and significant increase in hydroalcohalic extact of roots of Boerhavvia diffusa by
tail flick latency in case of combination with respect to piperine (10 and 20mg). Hepatotoxicity was induced by
control. The findings suggest that the Piper nigrum CCl4 and rifampicin isoniazid combination and effect
extract significantly increased the analgesic activity of of piperine evident by reduction in serum glutamate
diclofenac sodium and pentazocine.[44] pyruvate transaminase, serum glutamate oxaloacetate
Badmaev V, et al., (2000) found the nonspecific transaminase, and alkaline phosphatase in both
bioenhancing effect of piperine (5 mg) when it was cases.[49]
increase the plasma levels of supplemental coenzyme Bano G, et al., (1991) examined the effect of piperine
Q10 in a clinical study using a double-blind design. The (20 mg) on the bioavailability and pharmacokinetics of
relative bioavailability of 90 mg and 120 mg of propranolol (40 mg) and theophylline (150 mg) in a
coenzyme Q10 administered in a single-dose crossover study for 7 days. Result showed an earlier
experiment or in separate experiments for 14 and 21 tmax and a higher Cmax and AUC in the subjects who
days with placebo or with 5 mg of piperine was received piperine and propranolol and a higher Cmax,
determined by comparing measured changes in plasma longer elimination half-life and a higher AUC in case of
concentration. The results of the single-dose study and theophylline with piperine.[50]
the 14-day study indicate smaller, but not significant, Johnson JJ, et al., (2011) examined the effect of piperine
increases in plasma concentrations of coenzyme Q10 (10 mg/kg) on pharmacokinetic parameters of
but supplementation of 120 mg coenzyme Q10 with resveratrol (100 mg/kg) in mice. Serum levels of
piperine for 21 days produced approximately 30% resveratrol and resveratrol-3-O--D-glucuronide were
greater, area under the plasma curve than was analyzed at different times and they found that AUC of
observed during supplementation with coenzyme Q10 resveratrol was enhanced to 229% and the maximum
plus placebo.[45] serum concentration (Cmax) was increased to 1544%
Badmaev V, et al., (1999) evaluated the effectiveness of with the addition of piperine.[51]
piperine (5 mg) to improve serum response of beta- Janakiraman K, et al., (2008) found that co-
carotene (15 mg) during oral supplementation using a administration of Piperine (20mg/kg) enhanced oral

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bioavailability of Ampicillin and Norfloxacin in animal enzyme system and thereby potentiates the
model. This is reflected in various pharmacokinetic pentobarbitone sleeping time.[58]
measurements like Cmax, Tmax, AUC and t of the above Patel S, et al., (2011) studied the influence of co-
antibiotics in animal model.[52] administration of piperine (15 mg/kg) on
Hiwale A R, et al., (2002) found that co-administration pharmacokinetic profile of single dose of gatifloxacin
of piperine enhanced bioavailability of beta lactam (10 mg/kg body weight) in layer birds. The study
antibiotics, amoxycillin trihydrate and cefotaxime revealed that piperine significantly enhances the
sodium significantly in rats. The improved bioavailability of gatifloxacin from 74.52 1.021% to
bioavailability is reflected in various pharmacokinetic 85.74 0.956% as compared to control group. The
parameters viz. tmax, Cmax, t(1/2) and AUC, of these results thus obtained were the combined effect of
antibiotics. The increased bioavailability could be piperine on the absorption kinetics and the inhibition
attributed to the effect of piperine on microsomal of the metabolism of gatifloxacin.[59] Devada SS, et al.,
metabolising enzymes or enzymes system.[53] (2011) observed similar effects in broiler birds where
Lambert JD, et al., (2004) reported that the piperine piperine enhances the bioavailability of same drug
(70.2mol/kg) increases the Cmax and AUC of from 72.96 1.10 % to 81.95 1.56 % compared to
Epigallocatechin-3-gallate (EGCG) (163.8 mol/kg) by gatifloxacin alone treated group.[60]
1.3-fold compared to mice (intragastric administration) Singh A, et al., (2011) treated the male New Zealand
treated with EGCG alone. They demonstrated that white rats with atenolol (100 mg/kg) and combination
Piperine (100mol/L) inhibited EGCG glucuronidation in of atenolol and piperine (10 mg/kg). They found that
mouse small intestine (by 40%) and also inhibited bioavailability of atenolol was significantly enhance in
production of EGCG-3_-glucuronide in human HT-29 the presence of piperine.[61] Singh A, et al., (2012) found
colon adenocarcinoma cells. The appearance of EGCG in similar bioenhancing effect when they treated male
the colon and the feces of piperine-cotreated mice was New Zealand white rats with Losartan potassium (100
slower than in mice treated with EGCG alone.[54] mg/kg) and combination of Losartan potassium and
Khan I A, et al., (2006) found that piperine in piperine (10 mg/kg).[62]
combination with ciprofloxacin markedly reduced the Bhardwaj RK, et al., (2002) investigated the influence of
MICs and mutation prevention concentration of piperine on P-glycoprotein-mediated, polarized
ciprofloxacin for Staphylococcus aureus, including transport of digoxin and cyclosporine in monolayers of
methicillin resistant S. aureus. The enhanced Caco-2 cells and also the effect of piperine on CYP3A4-
accumulation and decreased efflux of ethidium mediated formation of the verapamil metabolites D-
bromide in the wild-type and mutant (CIPr-1) strains in 617 and norverapamil by using human liver
the presence of piperine suggest its involvement in the microsomes. Piperine inhibited digoxin and
inhibition of bacterial efflux pumps.[55] cyclosporine A transport in Caco-2 cells with IC50
Pattanaik S, et al., (2006) explore the effect of a single values of 15.5 and 74.1 _M, respectively. CYP3A4-
dose of piperine (20 mg) in patients with uncontrolled catalyzed formation of D-617 and norvera3pamil was
epilepsy on the steady-state pharmacokinetics of inhibited in a mixed fashion, with Ki values of 36 8
phenytoin (150 mg or 200 mg twice daily). Blood (liver 1)/49 6 (liver 2) and 44 10 (liver 1)/77 10
samples were collected and analyzed at regular _M (liver 2), respectively. They showed that piperine
interval. There was a significant increase in AUC, Cmax. inhibits both the drug transporter P-glycoprotein and
The results showed that piperine enhanced the the major drug-metabolizing enzyme CYP3A4. [63]
bioavailability of phenytoin significantly, possibly by Venkatesh S, et al., (2011) studied the influence of
increasing the absorption of the phenytoin.[56] piperine (10 mg/kg) on ibuprofen induced
Gupta SK, et al., (1998) found that the plasma antinociception and its pharmacokinetics. Piperine was
concentration of nimesulide (10 mg/kg) was increased significantly increase the plasma concentration and
from 8.03 0.99 ug/ mL to 11.90.23 ug/mL after the dose-dependent antinociceptive activity of ibuprofen
coadministration of nimesulide with piperine (10 evaluated by both acetic acid writhing and formalin
mg/kg). This indicates that piperine inhibits the test, when it was administered with ibuprofen. From
biotransformation and metabolism of nimesulide this study it can be concluded that piperine can be used
which leads to higher levels of drug in the systemic as a bioenhancer along with ibuprofen.[64]
circulation. [57] MARKETED PRODUCT OF PIPERINE AS
Mujumdar AM, et al., (1990) studied the effect of BIOENHANCER WITH DRUG
piperine on pentobarbitone induced hypnosis in rats. Risorine is a formulation developed by Indian Institute
Piperine potentiated the pentobarbitone sleeping time, of Integrative Medicine, Jammu, and marketed in India
as compared to the controls. They concluded that it is in November 2009 in publicprivate partnership with
possible that, piperine inhibits liver microsomal Cadila Pharmaceutical Ltd, Ahmedabad. Risorine has

Asian Journal of Biomedical and Pharmaceutical Sciences, all rights reserved. Volume 4, Issue 36, 2014. 6
 Shailendra Wadhwa et al: Asian Journal of Biomedical and Pharmaceutical Sciences; 4(36) 2014, 1-8.

been approved for marketing by Drug Controller 9. Evans WC. Trease and Evans' Pharmacognosy, 14th edn. W. B.
General of India, after successful completion of all the Saunders, London, 1997:36364.
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