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Dear readers,
Someone knows if P-glycoprotein could have some effect on Tmax besides
oral bioavailability
Any thoughts would be appreciated
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[A few replies - db]
From: "Gobburu, Jogarao V"
Date: Tue, 11 Dec 2001 13:40:16 -0500
To: david.-a-.boomer.org
Subject: RE: PharmPK P-glycoprotein
The following message was posted to: PharmPK
Hello,
It is possible that p-glycoprotein back transports drug molecules into the
gut lumen, thereby the affecting Tmax besides bioavailability.
Regards,
Joga Gobburu,
Pharmacometrics,
CDER, FDA
---
From: "Sreenivasa Rao Vanapalli"
Date: Tue, 11 Dec 2001 13:15:40 -0800
To: david.-a-.boomer.org
Subject: RE: PharmPK P-glycoprotein
The following message was posted to: PharmPK
Dear Fernandez
P-glycoprotein has effect on Tmax too in addition to bioavailability. You
can see the results of a study on the effect of verapamil (a strong
P-glycoprotein substrate)on talinolol pharmacokinetics. In this study the
authors found Tmax of talinolol decreased from 3 hours to approximately 1
hour after administering with verapamil. Here is the reference...
"Unexpected effect of verapamil on oral bioavailability of the beta-blocker
talinolol in humans"
Ute I.Schwarz et al., Clinical Pharmacology & Therapeutics 65(3):283-290
(March 1999)
thanks
Sreenivasa Rao Vanapalli, Ph.D.,
Janssen Postdoctoral Research Scholar,
S411 PHAR, College of Pharmacy, Univesrsity of Iowa,
Iowa City, IA-52242
---
From: Charo Calvo
Date: Wed, 12 Dec 2001 12:37:07 +0100
To: david.-at-.boomer.org
Subject: Re: PharmPK P-glycoprotein
The following message was posted to: PharmPK
Hello Raquel,
Yes. P-gp can influence Tmax. A good reference is:
Induction of P-glycoprotein by rifampin increases intestinal secretion of
talinolol in human beings: a new type of drug/drug interaction.
Westphal K, Weinbrenner A, Zschiesche M, Franke G, Knoke M, Oertel R, Fritz
P, von Richter O, Warzok R, Hachenberg T, Kauffmann HM, Schrenk D, Terhaag
B, Kroemer HK, Siegmund W.
Clin Pharmacol Ther. 2000 Oct;68(4):345-55.
Regards,
Charo
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The following message was posted to: PharmPK
you may also want to consider single nucleotide polymorphisms (SNPs) in the
multi drug resistant 1 (MDR1) gene that codes for P-glycoprotein and observe
if a percentage of your patients have increased or decreased Tmax or F.
Glenn Whelan, PharmD, Research Fellow
Nemours Children's Clinic
807 Children's Way
Jacksonville, FL 32250
Phone 904.390.3406
Fax 904.390.3425
email gwhelan.at.nemours.org
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