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The following message was posted to: PharmPK
Dear all,
It is a common practice that in a fasted-state BA/BE study, the
subject(s)
are administered the first post-dose meals (generally lunch) after
about 4
hours of administration of the investigational product.
What is the basis of this figure of 4 hours, can this be increased to
5 or
6 hours ?
Thanks & Regards,
V. Madhuri,
India
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The following message was posted to: PharmPK
It probably has to do with the fact subjects take the medication
around 8am and lunch is maybe around 12am
Hans
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Dear Madhuri,
You can increase it to 5 or 6 hours, as the 4 hours stated by the
guidelines is a minimum requirement.
I believe this 4 hours was decided to ensure that majority of the
drug's absorption is over and the drug leaves the stomach before it is
interfered by the food consumed (eventhough the gastric emptying time
is less than 2 hours in normal volunteers), which will fulfill the
objective of a fasting study.
Regards
Dr. M. Joseph
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Hi Madhuri
The pattern of 4 hours post dose lunch is because of the following
reasons:
1. The dosing occurs at 8 am or 9 am so, the lunch time falls
eventually at 12 to 1 pm. The subjects also feels hungry around that
time and will be able to consume the food.
2. If you want to provide lunch at 2- 3 hrs post dose, then, it might
affect the gastric emptying of the formulation from its usual way. It
is also advisable to follow the food time pattern of subjects in the
usual way (other than study specific requirements) they follow in
their daily life. In our BA-BE studies we intend to follow that
standardized pattern in all the periods of the study uniformly to
minimize the study process variations as much as possible.
3. If the dosing is planned at 6 or 7 am, then, very much the lunch
can be postponed to 5 or 6 hours. However, please bear in mind the
difficulty of study arrangements and study subjects convenience if a
dosing need to be done very early. (you should also provide the check-
in day dinner in such appropriate time to maintain at least 10 hours
fasting).
If your team feels that all the above objectives can be satisfied if
the lunch time is scheduled 5 or 6 hours post dose, then, you can very
well adopt that. There is no guidelines on the lunch, snacks and
dinner time on a single dose BA/BE study. The guidelines are mainly
concerned on the fasting duration, breakfast contents (fed study) and
uniformity of study conduct in all the periods.
I hope your query is answered.
Regards
V.Rajesh
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Dear Madhuri
In addition to the dosage form-related factors, bioavailability of
oral dosage form may also be affected by a variety of physiologic and
clinical factors related to the patient/subject. One example of the
myriad of physiologic factors that can affect the bioavailability of
an orally administered drug is a subject's gastric emptying rate.
Since the proximal small intestine is the optimum site for drug
absorption, a change in the stomach emptying rate is likely to alter
the rate, and possibly the extent, of drug absorption. Any factor that
slows the gastric emptying rate may thus prolong the onset time for
drug action and reduce the therapeutic efficacy of drugs that are
primarily absorbed from the small intestine. In addition, a delay in
gastric emptying could result in extensive decomposition and reduced
bioavailability of drugs that are unstable in the acidic media of the
stomach (e.g. penicillins and erythromycin).
There are numerous factors that affect gastric emptying rate. One of
them is food. Food can have a significant effect on the
bioavailability of drugs. Food may influence drug absorption
indirectly, through physiological changes in the GI tract produced by
the food, and/or directly, through physical or chemical interactions
between the drug molecules and food components. When food is ingested,
stomach emptying is delayed, gastric secretions are increased, stomach
pH is altered, and splanchnic blood flow may increase. These may all
affect bioavailability of drugs. Food may also interact directly with
drugs, either chemically (e.g. chelation) or physically, by adsorbing
the drug or acting as a barrier to absorption. In general,
gastrointestinal absorption of drugs is favored by an empty stomach.
Due to above complex reasons, generally food is given 4hrs post-dose
in BA/BE fasting study.[The gastric emptying time is about 2 hours in
normal individuals]. Also, you can give food once you complete 4hrs
post-dose. But please note that if food is given after 5-6 hrs, your
subjects may suffer from hypoglycemia because already they are on an
overnight fast of at least 10 hrs. For your information, I am
attaching a graph. [I got it from some article, don't remember now]
Thanks
Dr Sajjad A Desai
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Dear ms. Madhuri,
Normally, we are allowing 4 hours , but it is not fixed. We can go
upto 5 hours .
But, it is better, this deviation (is approved by the ethics
committee). Otherwise, you may get some querries fom regulatory
authorities.
T.R.Yegnaraman,
Manager-QA,
Azidus Laboratories Limited,
CRO division,
23, School Road,
Ratnamangalam
Vandalur-Kelambakkam Road,
chennai-600 048
India
mail : ryraman2661.at.yahoo.co.in, yegnaraman.-at-.azidus.com
www.azidus.com
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