Loading...
Please wait, while we are loading the content...
Similar Documents
A population pharmacokinetic model for disposition in plasma, saliva and urine of scopolamine after intranasal administration to healthy human subjects
| Content Provider | NASA Technical Reports Server (NTRS) |
|---|---|
| Author | Chow, D. S. L. Putcha, L. Wu, L. Tam, V. H. |
| Copyright Year | 2014 |
| Description | An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LCâMSâMS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (â2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal â2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The bestâfit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a nonâlinear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing nonâinvasive therapeutic monitoring of scopolamine in space and other remote environments. |
| File Size | 127308 |
| Page Count | 2 |
| File Format | |
| Alternate Webpage(s) | http://archive.org/details/NASA_NTRS_Archive_20140008723 |
| Archival Resource Key | ark:/13960/t5r83bm22 |
| Language | English |
| Publisher Date | 2014-01-01 |
| Access Restriction | Open |
| Subject Keyword | Aerospace Medicine Urine Motion Sickness Drugs Nose Anatomy Motion Sickness Models Pharmacology Bioavailability Dosage Saliva Blood Ntrs Nasa Technical Reports Server (ntrs) Nasa Technical Reports Server Aerodynamics Aircraft Aerospace Engineering Aerospace Aeronautic Space Science |
| Content Type | Text |
| Resource Type | Article |
