Population pharmacokinetic model of lithium and drug compliance assessment
Por:
Perez-Castello, I, Mangas-Sanjuan, V, Gonzalez-Garcia, I, Gonzalez-Alvarez, I, Bermejo, M, Marco-Garbayo, J and Troconiz, I
Publicada:
1 dic 2016
Resumen:
Population pharmacokinetic analysis of lithium during therapeutic drug monitoring and drug compliance assessment was performed in 54 patients and 246 plasma concentrations levels were included in this study. Patients received several treatment cycles (1-9) and one plasma concentration measurement for each patient was obtained always before starting next cycle (pre-dose) at steady state. Data were analysed using the population approach with NONMEM version 7.2. Lithium measurements were described using a two-compartment model (CL/F=0.41 L h(-1), V-1/F=15.3 L, Q/F=0.61 L h(-1), and V-2/F = 15.8 L) and the most significant covariate on lithium CL was found to be creatinine clearance (reference model). Lithium compliance was analysed using inter-occasion variability or Markovian features (previous lithium measurement as ordered categorical covariate) on bioavailability parameter. Markov-type model predicted the lithium compliance in the next cycle with higher success rate (79.8%) compared to IOV model (65.2%) and reference model (43.2%). This model becomes an efficient tool, not only being able to adequately describe the observed outcome, but also to predict the individual drug compliance in the next cycle. Therefore, Bipolar disorder patients can be classified regarding their probability to become extensive or poor compliers in the next cycle and then, individual probabilities lower than 0.5 highlight the need of intensive monitoring, as well as other pharmaceutical care measurements that might be applied to enhance drug compliance for a better and safer lithium treatment. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.
Filiaciones:
Perez-Castello, I:
Univ Miguel Hernandez Elche, Dept Engn, Mol & Cellular Biol Program, Carretera Alicante Valencia Km 87, Alicante 03550, Spain
Hosp Francesc de Borja, Dept Clin Pharm, Av Med 6, Valencia 46702, Spain
Mangas-Sanjuan, V:
Univ Miguel Hernandez Elche, Dept Engn, Mol & Cellular Biol Program, Carretera Alicante Valencia Km 87, Alicante 03550, Spain
Univ Navarra, Dept Pharm & Pharmaceut Technol, Pharmacometr & Syst Pharmacol, Sch Pharm, Irunlarrea 1, Pamplona 31008, Navarra, Spain
Gonzalez-Garcia, I:
Univ Valencia, Pharm & Pharmaceut Technol Dept, Av Vicent Andres Estelles S-N, E-46100 Valencia, Spain
PharmaMar, Clin Pharmacol, Madrid, Spain
Gonzalez-Alvarez, I:
Univ Miguel Hernandez Elche, Dept Engn, Mol & Cellular Biol Program, Carretera Alicante Valencia Km 87, Alicante 03550, Spain
Bermejo, M:
Univ Miguel Hernandez Elche, Dept Engn, Mol & Cellular Biol Program, Carretera Alicante Valencia Km 87, Alicante 03550, Spain
:
Hosp Francesc de Borja, Dept Clin Pharm, Av Med 6, Valencia 46702, Spain
Troconiz, I:
Univ Navarra, Dept Pharm & Pharmaceut Technol, Pharmacometr & Syst Pharmacol, Sch Pharm, Irunlarrea 1, Pamplona 31008, Navarra, Spain
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