Population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (recombinant exendin-4, rE-4) in Chinese patients with type 2 diabetes mellitusâ©.
Int J Clin Pharmacol Ther
; 55(8): 650-658, 2017 Aug.
Article
in En
| MEDLINE
| ID: mdl-28513427
ABSTRACT
OBJECTIVE:
To investigate the population pharmacokinetics of lyophilized recombinant glucagon-like peptide-1 receptor agonist (rE-4) in Chinese patients with type 2 diabetes mellitus (T2DM) for plasma concentration estimation and individualized treatment.METHODS:
Twelve patients with T2DM were enrolled to receive subcutaneous injections of rE-4 at 5 µg twice daily for 84 days. Administration dosage was adjusted from 5 µg to 10 µg twice daily at day 29 in case of glycated albumin (GA) ≥ 17%. The population pharmacokinetic model was developed in the nonlinear mixed-effects modeling software NONMEM.RESULTS:
The data were best described by a two-compartment model with first-order absorption and elimination. The outcome parameters were as follows apparent clearance (CL/F) 6.67 L/h, apparent distribution volume of central compartment (Vc/F) 19.4 L, absorption rate constant (Ka) 1.39 h-1, apparent distribution volume of peripheral compartment (Vp/F) 22.6 L, intercompartmental clearance (Q/F) 1.28 L/h. The interindividual variabilities for CL/F, Vc/F, Ka, and Q/F were 64.4%, 57.7%, 45.5%, and 153.3%, respectively. The intra-individual variability of proportional error model was 41.7%. No covariate was screened out that showed significant influence on the model parameters.CONCLUSIONS:
The established two-compartment model with first-order absorption and elimination successfully described the pharmacokinetic characteristics of rE-4 in Chinese patients with T2DM.â©.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Venoms
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Diabetes Mellitus, Type 2
/
Glucagon-Like Peptide-1 Receptor
Type of study:
Prognostic_studies
Limits:
Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Int J Clin Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2017
Type:
Article