Bioequivalence and Bioavailability Forum

Dear Tarak!

❝ now the question was why 1 hr before dosing and 1 hr after dosing water restriction.

❝ so in my opinion, as per pharmacokinetic and what we learned in medicine, water will do the distention of stomach which results in increase in surface area and thats why increases the absorption.

Sorry, IMHO this is not the case for the following reasons:

1. In fasted state only 50 ml – 350 ml[/nb of the average volume of [nb]1500 ml are filled with liquid (where the distribution of volumes is verly likely skewed towards 50 ml), therefore no distention is to be expected,
   
2. the stomach is not an absoption site for most drugs (except for ethanol), and
   
3. even if we assume a neutral molecule, which would be equally absorbed throughout all pH-ranges (i.e., the entire GIT-tract would act as an absorption window), the stomach would play no significant role, since surface areas are 0.06 m² (stomach), 2 m² (duodenum), 180 m² (jejunum), 280 m² (ileum), and 1.5 m² (colon).

❝ To maintain similarity guideline says only 240 ml of water should be given at the time of dosing. but if it is given less, then you have to mention protocol deviation and just to evaluate the PK parameters afterwards.

Suggested water volumes vary according to different guidelines within 100 ml – 250 ml (see this post).

❝ still que is there why only 240ml???

Following the baseless rumour, that patients take their medication together with the (US) standard cup of water.
I don’t know of a single study comparing plasma concentrations of any IR formulation administered with 240 ml v.s. a different volume.
BTW, according to the short average gastric emptying time of water in the stomach (15 minutes, see references), differences in volume would quickly level out anyway.

It’s nice that many colleagues follow the American roadshow (8 fluid ounces) unquestioned, but in the worlds largest economic area (the European Union based on GPD, 493 Mio citizens), Canada, Japan, and many other countries (not forgetting the WHO!), only 150ml are recommend…

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References (Scintigraphy, epigastric impedance technique, or real time ultrasound measurements: values given for healthy controls)
Murphy, D.B., Sutton, J.A., Prescott, L.F., Murphy, M.B.
Opioid-induced Delay in Gastric Emptying: A Peripheral Mechanism in Humans
Anesthesiology. 87(4):765-770 (October 1997)
500 ml water (n=11): 5.5 ± 2.1 min
Murphy, D.B., Sutton, A., Prescott, L.F., Murphy, M.B.
A comparison of the effects of tramadol and morphine on gastric emptying in man
Anaesthesia. 52(12):1224-1229 (December 1997)
500 ml water (n=11): 7.7 ± 3.3 min
Chang, F.Y., Lu, C.L., Chen, C.Y., Lee, S.D., Tsai, D.S., Fu, S.E.
The Pharmacological Effect of Omeprazole on Water Gastric Emptying: A Study Based on an Impedance Measure
Pharmacology 63:50-57 (2001)
500ml water (n=15): 12.7 ± 5.1 min
Chang F.Y., Chen C.Y., Lu C.L., Luo J.C., Jiun K.L., Lee S.D., Wu C.W.
Undisturbed water gastric emptying in patients of stomach cancer
Hepatogastroenterology 51(58):1219-24 (2004 Jul-Aug)
500 ml water (n=28): 16.8 ± 2.1 min
J.F. Pedersen
Sonographic Comparison of Gastric Emptying of Broth and Water: Is There a Promoting Cephalic Factor?
Health Science, Cancer and Oncology and Medical Research 46(2):132-134 (April 2005)
350 ml water (n=12): 20.3 min (range 12–40)