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A strange PK profile of an oral formulation #554

Closed wangwei1619 closed 4 years ago

wangwei1619 commented 4 years ago

Hi, all

Recently I have recived a PK result of a single administraiton of an oral formulation with, like this: image The absorption peak which should exist in first several hours seems disappeared in this figure. However, the first data point was measured at 0.5 h, which may result in absorption peak not recorded. I think the figure is strange because drug is meatabolized quickly according to the profile before 15 h, but curve after 20 h seems to say it is not. Besides, how is the second peak formed, by enterohepatic circulation? Is it normal for a peak caused by enterohepatic circulation to be so high? And is there any else potential reason to explain this phenomenon?

Thanks for comments.

tobiasK2001 commented 4 years ago

Yes, indeed this looks strange and leaves more questions than answers. From the time course it looks like we have strong colonic absorption here. I guess we are in human? EHC peaks tend to occur after the first meal after dose e.g. 3-4 hours after last dose. Tablets are immediate release or controlled release? Compound is BCS 2 or 4?

wangwei1619 commented 4 years ago

Oh, I should say this is data from beagle dogs. The chemical is lycopene, but it is formulated with PEG so that solubility is exceeding 800 ug/mL and it dissolves fast, but I don't know the exact permeability because I didn't receive such data. Is there any example of formulation behaving like this?

RobinM92 commented 4 years ago

If it is lycopene, are both the trans and cis form measured or only one of the two? As the cis-isoform accumulates into micelles in vivo.

Kind regards,

Robin

Dr. ir. Robin Michelet Senior scientist

Freie Universitaet Berlin Institute of Pharmacy Dept. of Clinical Pharmacy & Biochemistry Kelchstr. 31 12169 Berlin Germany Phone: + 49 30 838 50659 Fax: + 49 30 838 4 50656 Email: robin.michelet@fu-berlin.de www.clinical-pharmacy.eu REGISTER NOW! 9th International Microdialysis Symposium; early bird: -15 May 2020

On 22-06-20 9:53 AM, Wang Wei wrote:

Oh, I should say this is data from beagle dogs. The chemical is lycopene, but it is formulated with PEG so that solubility is exceeding 800 ug/mL and it dissolves fast, but I don't know the exact permeability because I didn't receive such data. Is there any example of formulation behaving like this?

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wangwei1619 commented 4 years ago

Hi, Robin

In fact, I don't know which type this lycopene is of. We have suspened this modeling work since we don't have enough supporting data. But, I still think this is a interesting example that I can keep in mind.

Thanks for your help.

Best regards, Wamg Wei

Yuri05 commented 4 years ago

@wangwei1619 Closing. Please reopen if there are still any unanswered questions.