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Hi everybody,
Happy New Year!
One question for fresh start.
I go results from BE study under fed conditions. Individual
concentration-time curves are quite demanding.
Plasma concentrations are fluctuating and second peak appears,
although it wasn't so notable under fasting conditions.
Tmax has a wide range over 22 hours.
This drug is metabolized in the liver and eliminated from the body by
urine, so recirculation is not an option.
1. Just give me few options why would second peak occur under fed
conditions and not under fasting?
Is it possible that this drug has two sites of absorption and as this
drug has a higher availability under fed conditions that a higher
amount of dissolved drug comes to the second absorption site and the
second pik is more clear.
2. If physiology and PK of his drug is not the cause of this, maybe
you can also give me some suggestions what would be a possible reason?
Thank in advance,
Lidija
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This article might help.
Appearance of Double Peaks in Plasma Concentration-time Profile after
Oral Administration Depends on Gastric Emptying Profile and Weight
Function Pharm Res. 2007 Oct 23
Eyob
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Hi,
Another article which might help:
Dedik, L., Durisova, M., Penesova, A., Miklovicova, D., Tvrdonova,
M.: Estimation of influence of gastric emptying on shape of glucose
concentration-time profile measured in oral glucose tolerance test,
Diab Res Clin Prac, 77, 2007, 377-384.
With best regards,
Maria Durisova DSc (Math/Phys)
www.uef.sav.sk/durisova.htm
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Hi,
A few reasons can cause double peaks one of which was suggested by a
colleague (delaye gastric emptying).
GI transit time or an absorption window effect could also give rise to
the double-peak phenomenon. Differential or sequential absorption of
unchanged drug and its metabolites or simply of different metabolites
could sometimes also result in the occurrence of the double peak.
Progressive solubilization along the GI tract and its subsequent
intestinal absorption may also contribute to the double peak profile.
Some authors postulated that the double peak phenomenon could be
accounted for by two distinct absorption sites for the drug, which
are separated by a region of relatively low absorption. Sometimes,the
pharmacological effect of the drug of interest could also play a role
in the formation of the double peak. Wang et al hypothesized that the
double-peak phenomenon of alprazolam following oral administration was
due to the reduction in gastric motility caused by the muscle relaxant
effect of alprazolam itself.
Some references that may be helpful are below:
1.*Veng Pedersen P: Pharmacokinetic analysis by linear system
approach: I. Cimetidine bioavailability and second peak phenomenon. J
Pharm Sci 1981;70:32-38.
2.Beerman B: Value of plasma digoxin estimation. Lancet 1973;1:375.
3.Parquet M, Metman EH, Raizman A, Rambaud JC, Berthaux N, Infante R:
Bioavailability, gastrointestinal transit, solubilization and faecal
excretion of urosodeoxycholic acid in man. Eur J Clin Invest
1985;15:171-178.
4. PlusquellecY, Campistron G, Staveris S, Barre J, Jung L,Tillement
JP, Houin G: A double-peak phenomena in the pharmacokinetics of
veralipride after oral administration: a double-site model for drug
absorption. J Pharmacokinet Biopharm 1987;15:225-239.
5.WangY, Roy A, Sun L, Lau CE:Adouble-peak phenomenon in the
pharmacokinetics of alprazolam after oral administration. Drug Metab
Dispos 1999;27(8):855-859.
I hope this is of some assistance.
Murad Melhem
Assistant Director
Cognigen Corporation
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Dear Koren,
Is your drug highly water soluble?
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The following message was posted to: PharmPK
Dear Chakradhar,
No, drug is practically insoluble in water.
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The following message was posted to: PharmPK
Dear Chakradhar,
No, drug is practically insoluble in water.
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