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Population Pharmacokinetic Model to Assess the Impact of Disease State on Thalidomide Pharmacokinetics.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2020 Jan; Vol. 60 (1), pp. 67-74. Date of Electronic Publication: 2019 Aug 07. - Publication Year :
- 2020
-
Abstract
- A population pharmacokinetic (PPK) model to describe the pharmacokinetics of thalidomide in different patient populations was developed using data pooled from healthy subjects and patients with Hansen's disease, human immunodeficiency virus (HIV), and multiple myeloma (MM). The analysis data set had a total of 164 evaluable subjects who received various doses (50 to 400 mg) of oral thalidomide in single- and/or multiple-dose regimens. The plasma thalidomide concentrations were adequately described by a linear 1-compartment PPK model with first-order absorption and first-order elimination. Inclusion of MM as a covariate on apparent clearance (CL/F) accounted for 4.4% of the interindividual variability (IIV) of CL/F. Body weight as a covariate on CL/F and apparent volume of distribution (V/F) also improved model fitting slightly, accounting for 7.2% and 20% of IIV, respectively. Although inclusion of body weight and MM as covariates of CL/F and body weight on V/F improved the goodness of fit of the model in a statistically significant manner, the impact of this difference in CL/F is not considered clinically relevant. Other factors such as age, sex, race, creatinine clearance, and alanine transaminase had no effect on thalidomide pharmacokinetics. MM, HIV, and Hansen's disease have no clinically relevant effect on thalidomide disposition relative to healthy volunteers.<br /> (© 2019, The American College of Clinical Pharmacology.)
- Subjects :
- Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Drug Administration Schedule
Female
HIV Infections drug therapy
Healthy Volunteers
Humans
Immunosuppressive Agents administration & dosage
Immunosuppressive Agents blood
Immunosuppressive Agents therapeutic use
Leprosy drug therapy
Male
Metabolic Clearance Rate
Middle Aged
Models, Biological
Multiple Myeloma drug therapy
Thalidomide administration & dosage
Thalidomide blood
Thalidomide therapeutic use
Young Adult
HIV Infections metabolism
Immunosuppressive Agents pharmacokinetics
Leprosy metabolism
Multiple Myeloma metabolism
Thalidomide pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 60
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31392755
- Full Text :
- https://doi.org/10.1002/jcph.1506