Population Pharmacokinetic Model to Assess the Impact of Disease State on Thalidomide Pharmacokinetics
| Autor: | Renfang Hwang, Maria Palmisano, Allison Gaudy, Nianhang Chen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Metabolic Clearance Rate Population Administration Oral Renal function HIV Infections Models Biological 030226 pharmacology & pharmacy Gastroenterology Drug Administration Schedule Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Leprosy Internal medicine Covariate medicine Humans Pharmacology (medical) education Multiple myeloma Aged Aged 80 and over Pharmacology Volume of distribution education.field_of_study biology business.industry Middle Aged medicine.disease Healthy Volunteers Thalidomide Alanine transaminase 030220 oncology & carcinogenesis biology.protein Female Multiple Myeloma business Immunosuppressive Agents medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 60:67-74 |
| ISSN: | 1552-4604 0091-2700 |
| DOI: | 10.1002/jcph.1506 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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