RE: PAMAM-OH nanoparticles

From: [email protected] [mailto:[email protected]] On Behalf Of Olinto Linares Sent: Thursday, June 02, 2011 3:31 PM To: [email protected] Cc: [email protected] Subject: RE: [NMusers] PAMAM-OH nanoparticles Thanks Matt for the suggestion. I am looking it. Dear Martin, 5 mice were scarified at any sample time to quantify the BioD of PAMAM-OH in all main organs ( brain, heart, lungs . .etc), so we have these data points at the sample times for a "future" Whole Body PBPK model? We have different nanoparticles data (HPMA, PAMAM, gold nanoparticles) but sampled with the same method ( the animal were sacrificed at the sample time). Following the paper suggested by Matt, could we do kinetics analysis only with a sample/animal? How robust will be those results? How we can work on the nanoparticle kinetics with these data? Best regards Olinto From: Martin Bergstrand [mailto:[email protected]] Sent: Thursday, June 02, 2011 12:38 PM To: [email protected]; [email protected] Subject: RE: [NMusers] PAMAM-OH nanoparticles Dear Olinto, I do not think that your suggestion on grouping the observations as if they originated from only five different mice is a good idea. How would you then interpret the random effects? What mice would be grouped together? However I wonder, cannot the nanoparticles be quantified in plasma and wasn't that sampled in any mice up until the sacrificing? The plasma PK of the nanoparticles should if I don't completely misunderstand the project be closely related to the biodistribution in one or several organs/tissues. If multi sample plasma PK and single sample tissue concentration was modeled simultaneous a large part of the problem with single sample tissue observations could be avoided. You likely still couldn't separate the between mice variability in any parameter exclusively describing the rate of a tissue distribution from the residual error (unless you make some fairly strong assumptions regarding the residual error) however the variability in tissue concentration will likely be largely dependent on variability in processes also affecting the plasma concentrations. Kind regards, Martin Bergstrand, PhD Pharmacometrics Research Group Dept of Pharmaceutical Biosciences Uppsala University Sweden Postal address: Box 591, 751 24 Uppsala, Sweden Phone +46 709 994 396 Fax + 46 18 4714003 From: [email protected] [mailto:[email protected]] On Behalf Of Fidler,Matt,FORT WORTH,R&D Sent: Thursday, June 02, 2011 7:43 PM To: [email protected]; [email protected] Subject: RE: [NMusers] PAMAM-OH nanoparticles Olinto, Hing et al reported using mixed-effect modeling instead of fixed effects modeling to characterize data (and may reduce parameter bias). However, this method still does not characterize between animal variability. Matt. Hing, J. P.; Woolfrey, S. G.; Greenslade, D. & Wright, P. M. Is mixed effects modeling or naïve pooled data analysis preferred for the interpretation of single sample per subject toxicokinetic data? J Pharmacokinet Pharmacodyn, Department of Anaesthesia, University of Newcastle upon Tyne and Alnwick Research Centre, Sanofi, Alnwick, Northumberland., 2001, 28, 193-210 From: [email protected] [mailto:[email protected]] On Behalf Of Olinto Linares Sent: Thursday, June 02, 2011 12:04 PM To: [email protected] Cc: [email protected] Subject: [NMusers] PAMAM-OH nanoparticles Dears NMusers PAMAM Nanoparticles used as anticancer drug carrier. During a biodistribution study 5 mice were sacrificed at each sample time, 5, 30, 60, 120 minutes, and 6, and 24 hours, after a bolus infusion of 50mg/kg of PAMAM-OH. We are interested in the PAMAM-OH kinetics. Can we apply population pharmacokinetics analysis on these types of data? (i.e grouping the data as if they came from only 5 mice that were sampled at those times)? looking for ideas, suggestions ________________________________ This e-mail (including any attachments) is confidential and may be legally privileged. If you are not an intended recipient or an authorized representative of an intended recipient, you are prohibited from using, copying or distributing the information in this e-mail or its attachments. If you have received this e-mail in error, please notify the sender immediately by return e-mail and delete all copies of this message and any attachments. Thank you. ________________________________ This e-mail (including any attachments) is confidential and may be legally privileged. If you are not an intended recipient or an authorized representative of an intended recipient, you are prohibited from using, copying or distributing the information in this e-mail or its attachments. If you have received this e-mail in error, please notify the sender immediately by return e-mail and delete all copies of this message and any attachments. Thank you.