Ana Catalán-Latorre, Amparo Nácher, Virginia Merino, N. VÃctor Jiménez-Torres, Matilde Merino-Sanjuán
Pharmacy and Pharmaceutical Technology Department, University of Valencia (Spain)
Objectives: It has been established that 5-15% of the general population, 40% of patients admitted to hospital and 60% of nursing home residents in the European Community are malnourished or at risk of malnutrition1, 2. Taurine, a conditionally essential aminoacid involved in numerous biological processes, is a regular component of commercial enteral diets provided to caquectic patients, although little is known about its pharmacokinetic (PK) from these formulations3. The aim of this study was to describe the behavior of taurine administered in two enteral commercial diets in well and undernourished rats and analyze the predictive capacity of a PK model developed in a previous study simulating WN and UN groups.
Methods: Wistar rats were randomly distributed in two groups – WN (well-nourished) and UN (undernourished) – and were fed with different pellet diets for 23-26 days4. During this time, weight was recorded daily and serum albumin was registered weekly. After this time, Isosource –ST™ and T-Diet Plus™ diets were orally (PO) administered to WN and UN rats (N=76). Plasma samples were collected for taurine and were analyzed by HPLC. The simulated concentrations were obtained by 100 simulations of WN and UN animals based on a previous developed two compartmental model using nonlinear mixed effects software (NONMEM 7.0)4. A visual predictive analysis was developed to determine if the PK model used reproduced the aminoacid plasma concentration in WN and UN groups.
Results: A two-compartment population PK model with zero order endogenous formation (Velo), passive absorption (ka), first order kinetics distribution (K12, K21) and nonlinear elimination with parallel Michaelis-Menten excretion and reabsorption processes best described taurine pharmacokinetics administrated as a solution. The main PK parameters are shown: ka=1.19 h-1, Velo=13.70 mg/h, Vc=0.042 l, K12=2.61 h-1, K21=0.73 h-1, Vmsec=192.0 mg/l·h-1 Kmsec=399.0 mg/l, Vmreabs=16.9 mg/l·h-1, Kmreabs=96.1 mg/l, FDNVms=0.91. Visual predictive check plots (VPC) after the administration of the doses of taurine contained in the enteral diets assayed showed reasonable good results.
Conclusions: Simulation of taurine plasma concentration provides a useful tool to describe the levels of taurine in well and under-nourished animals. This pre-clinical PK model also provides evidences to assess if the supplementation of taurine in enteral diets triggers an increment of taurine plasmatic concentrations.
References:
[1] Ray S, Laur C, Golubic R: Malnutrition in healthcare institutions: A review of the prevalence of under-nutrition in hospitals and care homes since 1994 in England, Clin Nutr 2013, http://dx.doi.org/10.1016/j.clnu.2013.1010.1017
[2] Garcia Rada A: Child poverty and malnutrition rise in Spain as austerity measures bite, BMJ 2013, 347:f5261
[3] Miyazaki T, Matsuzaki Y: Taurine and liver diseases: a focus on the heterogeneous protective properties of taurine, Amino Acids 2012, 46:101-110
[4] Merino-Sanjuan M, Catalan-Latorre A, Nacher A, Miralles-Arnau S, Jimenez-Torres NV: Animal model of undernutrition for the evaluation of drug pharmacokinetics, Nutr Hosp 2011, 26:1296-1304 [5] Ana Catalán-Latorre. [Modelización Farmacocinética de la Taurina: Evaluación del estado nutricional]. Universidad de Valencia, Spain, 2014c
Reference: PAGE 23 (2014) Abstr 3087 [www.page-meeting.org/?abstract=3087]
Poster: Drug/Disease modeling - Other topics