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THeMaCHinE
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Take your Nolvadex with GRAPEFRUIT JUICE for better effectivity
- Thread starter BigBazooka
- Start date
Thanks for all the info - don't trouble yourself anymore if you don't have it handy. I'm aware of the properties but was fuzzy on the mechanism and wondering whether the % increase in effectiveness with regards to blood levels was transferable to other oral AAS besides winstrol (var, dbol, etc..) or whether each substance might be enhanced to a different degree depending upon the structure.
THeMaCHinE
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It's no trouble -- I learn something every time I go back to look for something; I had no idea about the potential for the blocking of some drugs; I've not heard it ever discussed...
THeMaCHinE
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CB38AC said:
That's what I plan on using when appropriate. The pulp, the peels, the fruit itself are all thought to contain quercetin, naringin and naringenin, and 6 prime,7prime-dihydroxybergamottin -- the components suspected of inhibiting CYP3A4 activity.
THeMaCHinE
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Author
Jill M. Kolesar, Pharm. D.
School of Pharmacy
University of Wisconsin
Accreditation
The ACPE Number for this program 021-999-99-704-HO1 .
The University of Kansas School of Pharmacy Office of Postgraduate
Professional Education is approved by the American Council on Pharmaceutical
Education as a provider of continuing pharmaceutical education. This program is approved for 3
hour (0.3 CEUs).
Grapefruit Juice
Recently, attention has focused on the ability of grapefruit juice to increase the bioavalaibility of cyclosporine and calcium channel blockers via decreased activity of intestinal cytochrome P-450, specifically the CYP3A isoforms. The grapefruit juice components quercetin, naringin and naringenin, and 6 prime,7prime-dihydroxybergamottin have been studied for CYP3A inhibition without conclusively determining which component is responsible for the interaction.
Initial research focused on the ability of a component to bind to and inhibit CYP3A4 in the gastrointestinal lumen. A subsequent report has determined that this is actually a post transciptional regulatory event, resulting in decreased amount of CYP3A4 in the GI mucosa.
How clinically significant are interactions with grapefruit juice? It moderately decreases oral clearance of CYP3A substrates, some of which have a relatively narrow therapeutic index. It is an inhibitory interaction which may result in increased drug effect/toxicity at a given drug dose. However, the interaction occurs most reliably when either 8 oz of double-strength reconstituted grapefruit concentrate is taken with the drug substrate, or 8oz of regular strength grapefruit juice is taken three times a day.
This is a large amount of grapefruit juice to ingest making the occurrence low and less clinically significant. However, patients receiving immunosuppresion with cyclosporine represent a small subset of individuals where this interaction may be clinically important. This interaction may allow for a decreased amount of cyclosporine to achieve the same therapeutic effect, resulting substantial cost savings to the patient. It is reasonable to advise
patients receiving cyclosporine about the interaction and to avoid excessive grapefruit juice consumption, unless increased monitoring is performed.
Jill M. Kolesar, Pharm. D.
School of Pharmacy
University of Wisconsin
Accreditation
The ACPE Number for this program 021-999-99-704-HO1 .
The University of Kansas School of Pharmacy Office of Postgraduate
Professional Education is approved by the American Council on Pharmaceutical
Education as a provider of continuing pharmaceutical education. This program is approved for 3
hour (0.3 CEUs).
Grapefruit Juice
Recently, attention has focused on the ability of grapefruit juice to increase the bioavalaibility of cyclosporine and calcium channel blockers via decreased activity of intestinal cytochrome P-450, specifically the CYP3A isoforms. The grapefruit juice components quercetin, naringin and naringenin, and 6 prime,7prime-dihydroxybergamottin have been studied for CYP3A inhibition without conclusively determining which component is responsible for the interaction.
Initial research focused on the ability of a component to bind to and inhibit CYP3A4 in the gastrointestinal lumen. A subsequent report has determined that this is actually a post transciptional regulatory event, resulting in decreased amount of CYP3A4 in the GI mucosa.
How clinically significant are interactions with grapefruit juice? It moderately decreases oral clearance of CYP3A substrates, some of which have a relatively narrow therapeutic index. It is an inhibitory interaction which may result in increased drug effect/toxicity at a given drug dose. However, the interaction occurs most reliably when either 8 oz of double-strength reconstituted grapefruit concentrate is taken with the drug substrate, or 8oz of regular strength grapefruit juice is taken three times a day.
This is a large amount of grapefruit juice to ingest making the occurrence low and less clinically significant. However, patients receiving immunosuppresion with cyclosporine represent a small subset of individuals where this interaction may be clinically important. This interaction may allow for a decreased amount of cyclosporine to achieve the same therapeutic effect, resulting substantial cost savings to the patient. It is reasonable to advise
patients receiving cyclosporine about the interaction and to avoid excessive grapefruit juice consumption, unless increased monitoring is performed.
Also, piperine from black pepper extract (AKA bioperine) greatly enhances absorption of a diverse variety of drugs and chemicals, possibly via two separate mechanisms. You can find it at some supplement stores.
1: Planta Med 1998 May;64(4):353-6
Influence of piperine on the pharmacokinetics of curcumin in animals and human
volunteers.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
Department of Pharmacology, St. John's Medical College, Bangalore, India.
The medicinal properties of curcumin obtained from Curcuma longa L. cannot be
utilised because of poor bioavailability due to its rapid metabolism in the
liver and intestinal wall. In this study, the effect of combining piperine, a
known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the
bioavailability of curcumin in rats and healthy human volunteers. When curcumin
was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were
achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg
increased the serum concentration of curcumin for a short period of 1-2 h post
drug. Time to maximum was significantly increased (P < 0.02) while elimination
half life and clearance significantly decreased (P < 0.02), and the
bioavailability was increased by 154%. On the other hand in humans after a dose
of 2 g curcumin alone, serum levels were either undetectable or very low.
Concomitant administration of piperine 20 mg produced much higher concentrations
from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the
increase in bioavailability was 2000%. The study shows that in the dosages used,
piperine enhances the serum concentration, extent of absorption and
bioavailability of curcumin in both rats and humans with no adverse effects.
Publication Types:
Clinical Trial
PMID: 9619120 [PubMed - indexed for MEDLINE]
2: Indian J Exp Biol 1998 Jan;36(1):46-50
Permeability characteristics of piperine on oral absorption--an active alkaloid
from peppers and a bioavailability enhancer.
Khajuria A, Zutshi U, Bedi KL.
Isotope Section, Regional Research Laboratory, Jammu-Tawi, India.
Piperine, [1-[5-[1,3-benzodioxol-5-yl]-1-oxo-2,4, pentadienyl] piperidine], is a
pungent alkaloid present in Piper nigrum Linn, and P. longum Linn. It is shown
to enhance the bioavailability of various structurally and therapeutically
diverse drugs. A concise mechanism responsible for its bioavailability enhancing
action is poorly understood. This study is an effort to understand the
absorption dynamics of piperine in intestine on oral absorption. It encompasses
intestinal everted sacs as an experimental model. Cycloheximide treatment and
exclusion of Na+ salts from incubating medium were the variables used.
Absorption half life, absorption rate, absorption clearance and apparent
permeability co-efficient were computed from the data. Experiments to denote
physico-chemical characteristics of this moiety exhibited that it is a weak
base, highly lipophilic in nature with partial solubility in aqueous media. It
exhibited passive diffusion constituting non-saturable absorption kinetics.
Transport of piperine was not resisted by UWL and was proposed to be absorbed
through transcellular pathway. It displayed short absorption clearance and high
apparent permeability co-efficient. Data thus obtained suggested that piperine
is absorbed very fast across the intestinal barrier. It may act as an apolar
molecule and form apolar complex with drugs and solutes. It may modulate
membrane dynamics due to its easy partitioning thus helping in efficient
permeability across the barriers.
PMID: 9536651 [PubMed - indexed for MEDLINE]
3: Eur J Clin Pharmacol 1991;41(6):615-7
Effect of piperine on bioavailability and pharmacokinetics of propranolol and
theophylline in healthy volunteers.
Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK, Sharma SC.
Department of Pharmacology and Therapeutics, Government Medical College,
Jammu-Tawi, India.
The effect of piperine on the bioavailability and pharmacokinetics of
propranolol and theophylline has been examined in a crossover study. Six
subjects in each group received a single oral dose of propranolol 40 mg or
theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7
days. An earlier tmax and a higher Cmax and AUC were observed in the subjects
who received piperine and propranolol. It produced a higher Cmax, longer
elimination half-life and a higher AUC with theophylline. In clinical practice,
the enhanced systemic availability of oral propranolol and theophylline could be
exploited to achieve better therapeutic control and improved patient compliance.
PMID: 1815977 [PubMed - indexed for MEDLINE]
4: Planta Med 1987 Dec;53(6):568-9
The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers.
Bano G, Amla V, Raina RK, Zutshi U, Chopra CL.
PMID: 3444866 [PubMed - indexed for MEDLINE]
5: Toxicology 1986 Jul;40(1):83-92
Studies on the metabolism of piperine: absorption, tissue distribution and
excretion of urinary conjugates in rats.
Bhat BG, Chandrasekhara N.
Upon administration of piperine, the major bite factor of black pepper, to male
albino rats at a dose of 30 mg (170 mg/kg) by gavage or 15 mg (85 mg/kg)
intraperitoneally, about 97% was absorbed irrespective of the mode of dosing.
Three per cent of the administered dose was excreted as piperine in the feces.
Piperine was not detectable in urine. When everted sacs of rat intestines were
incubated with 200-1000 micrograms of piperine, about 47-64% of the added
piperine disappeared from the mucosal side. Only piperine was present in the
serosal fluid and also the intestinal tissue, indicating that piperine did not
undergo any metabolic change during absorption. Examination of the passage of
piperine through the gut indicated that the highest concentration in the stomach
and small intestine was attained at about 6 h. Only traces (less than 0.15%) of
piperine were detected in serum, kidney and spleen from 30 min to 24 h. About
1-2.5% of the intraperitoneally administered piperine was detected in the liver
during 0.5-6 h after administration as contrasted with 0.1-0.25% of the orally
administered dose. The increased excretion of conjugated uronic acids,
conjugated sulphates and phenols indicated that scission of the methylenedioxy
group of piperine, glucuronidation and sulphation appear to be the major steps
in the disposition of piperine in the rat.
PMID: 3715893 [PubMed - indexed for MEDLINE]
1: Planta Med 1998 May;64(4):353-6
Influence of piperine on the pharmacokinetics of curcumin in animals and human
volunteers.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS.
Department of Pharmacology, St. John's Medical College, Bangalore, India.
The medicinal properties of curcumin obtained from Curcuma longa L. cannot be
utilised because of poor bioavailability due to its rapid metabolism in the
liver and intestinal wall. In this study, the effect of combining piperine, a
known inhibitor of hepatic and intestinal glucuronidation, was evaluated on the
bioavailability of curcumin in rats and healthy human volunteers. When curcumin
was given alone, in the dose 2 g/kg to rats, moderate serum concentrations were
achieved over a period of 4 h. Concomitant administration of piperine 20 mg/kg
increased the serum concentration of curcumin for a short period of 1-2 h post
drug. Time to maximum was significantly increased (P < 0.02) while elimination
half life and clearance significantly decreased (P < 0.02), and the
bioavailability was increased by 154%. On the other hand in humans after a dose
of 2 g curcumin alone, serum levels were either undetectable or very low.
Concomitant administration of piperine 20 mg produced much higher concentrations
from 0.25 to 1 h post drug (P < 0.01 at 0.25 and 0.5 h; P < 0.001 at 1 h), the
increase in bioavailability was 2000%. The study shows that in the dosages used,
piperine enhances the serum concentration, extent of absorption and
bioavailability of curcumin in both rats and humans with no adverse effects.
Publication Types:
Clinical Trial
PMID: 9619120 [PubMed - indexed for MEDLINE]
2: Indian J Exp Biol 1998 Jan;36(1):46-50
Permeability characteristics of piperine on oral absorption--an active alkaloid
from peppers and a bioavailability enhancer.
Khajuria A, Zutshi U, Bedi KL.
Isotope Section, Regional Research Laboratory, Jammu-Tawi, India.
Piperine, [1-[5-[1,3-benzodioxol-5-yl]-1-oxo-2,4, pentadienyl] piperidine], is a
pungent alkaloid present in Piper nigrum Linn, and P. longum Linn. It is shown
to enhance the bioavailability of various structurally and therapeutically
diverse drugs. A concise mechanism responsible for its bioavailability enhancing
action is poorly understood. This study is an effort to understand the
absorption dynamics of piperine in intestine on oral absorption. It encompasses
intestinal everted sacs as an experimental model. Cycloheximide treatment and
exclusion of Na+ salts from incubating medium were the variables used.
Absorption half life, absorption rate, absorption clearance and apparent
permeability co-efficient were computed from the data. Experiments to denote
physico-chemical characteristics of this moiety exhibited that it is a weak
base, highly lipophilic in nature with partial solubility in aqueous media. It
exhibited passive diffusion constituting non-saturable absorption kinetics.
Transport of piperine was not resisted by UWL and was proposed to be absorbed
through transcellular pathway. It displayed short absorption clearance and high
apparent permeability co-efficient. Data thus obtained suggested that piperine
is absorbed very fast across the intestinal barrier. It may act as an apolar
molecule and form apolar complex with drugs and solutes. It may modulate
membrane dynamics due to its easy partitioning thus helping in efficient
permeability across the barriers.
PMID: 9536651 [PubMed - indexed for MEDLINE]
3: Eur J Clin Pharmacol 1991;41(6):615-7
Effect of piperine on bioavailability and pharmacokinetics of propranolol and
theophylline in healthy volunteers.
Bano G, Raina RK, Zutshi U, Bedi KL, Johri RK, Sharma SC.
Department of Pharmacology and Therapeutics, Government Medical College,
Jammu-Tawi, India.
The effect of piperine on the bioavailability and pharmacokinetics of
propranolol and theophylline has been examined in a crossover study. Six
subjects in each group received a single oral dose of propranolol 40 mg or
theophylline (150 mg) alone or in combination with piperine 20 mg daily for 7
days. An earlier tmax and a higher Cmax and AUC were observed in the subjects
who received piperine and propranolol. It produced a higher Cmax, longer
elimination half-life and a higher AUC with theophylline. In clinical practice,
the enhanced systemic availability of oral propranolol and theophylline could be
exploited to achieve better therapeutic control and improved patient compliance.
PMID: 1815977 [PubMed - indexed for MEDLINE]
4: Planta Med 1987 Dec;53(6):568-9
The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers.
Bano G, Amla V, Raina RK, Zutshi U, Chopra CL.
PMID: 3444866 [PubMed - indexed for MEDLINE]
5: Toxicology 1986 Jul;40(1):83-92
Studies on the metabolism of piperine: absorption, tissue distribution and
excretion of urinary conjugates in rats.
Bhat BG, Chandrasekhara N.
Upon administration of piperine, the major bite factor of black pepper, to male
albino rats at a dose of 30 mg (170 mg/kg) by gavage or 15 mg (85 mg/kg)
intraperitoneally, about 97% was absorbed irrespective of the mode of dosing.
Three per cent of the administered dose was excreted as piperine in the feces.
Piperine was not detectable in urine. When everted sacs of rat intestines were
incubated with 200-1000 micrograms of piperine, about 47-64% of the added
piperine disappeared from the mucosal side. Only piperine was present in the
serosal fluid and also the intestinal tissue, indicating that piperine did not
undergo any metabolic change during absorption. Examination of the passage of
piperine through the gut indicated that the highest concentration in the stomach
and small intestine was attained at about 6 h. Only traces (less than 0.15%) of
piperine were detected in serum, kidney and spleen from 30 min to 24 h. About
1-2.5% of the intraperitoneally administered piperine was detected in the liver
during 0.5-6 h after administration as contrasted with 0.1-0.25% of the orally
administered dose. The increased excretion of conjugated uronic acids,
conjugated sulphates and phenols indicated that scission of the methylenedioxy
group of piperine, glucuronidation and sulphation appear to be the major steps
in the disposition of piperine in the rat.
PMID: 3715893 [PubMed - indexed for MEDLINE]
RdStrcklnd
New member
Where are you guys getting the grapefruit extract, I hate that juice and its really fucking expensive.
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