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Pharmacometric characterization of a...

Ahn, Jae Eun.

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Pharmacometric characterization of antiepileptic drugs in the elderly.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Pharmacometric characterization of antiepileptic drugs in the elderly./
作者:	Ahn, Jae Eun.
面頁冊數:	140 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3075.
Contained By:	Dissertation Abstracts International67-06B.
標題:	Gerontology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3219968
ISBN:	9780542734496

Pharmacometric characterization of antiepileptic drugs in the elderly.
Ahn, Jae Eun.

Pharmacometric characterization of antiepileptic drugs in the elderly. - 140 p.

Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3075.

Thesis (Ph.D.)--University of Minnesota, 2006.

The incidence of epilepsy in the elderly is high and both community dwelling and nursing home residents are commonly treated with antiepileptic drugs. However, there is little information describing relationships among dose, concentrations, patient-specific characteristics, and response. Such information can be useful in determining appropriate doses when first initiating these drugs.

ISBN: 9780542734496Subjects--Topical Terms:

533633
Gerontology.

Pharmacometric characterization of antiepileptic drugs in the elderly.
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245 1 0 $a Pharmacometric characterization of antiepileptic drugs in the elderly.
300 $a 140 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-06, Section: B, page: 3075.
500 $a Advisers: Richard C. Brundage; Angela K. Birnbaum.
502 $a Thesis (Ph.D.)--University of Minnesota, 2006.
520 $a The incidence of epilepsy in the elderly is high and both community dwelling and nursing home residents are commonly treated with antiepileptic drugs. However, there is little information describing relationships among dose, concentrations, patient-specific characteristics, and response. Such information can be useful in determining appropriate doses when first initiating these drugs.
520 $a Pharmacokinetics (PK) of valproic acid and carbamazepine in elderly nursing home residents were estimated using nonlinear mixed effects modeling. NONMEM software was used for all data analyses. Estimated parameters include mean PK parameters, inter-individual variability associated with the parameters, and residual unexplained variability. Also, using forward inclusion and backward elimination approach, covariates which can explain the variability of clearance were identified and their effects were quantified. The final models were evaluated using a predictive check.
520 $a A potential problem with using therapeutic drug monitoring (TDM) data in population pharmacokinetic analyses was addressed. With TDM data, the relationship between dose and clearance is confounded, and dose is commonly determined incorrectly to be an important determinant of clearance. A Monte Carlo simulation was performed using NONMEM to demonstrate the problem and to estimate a statistical error rate (type II error) associated with a typical TDM scenario for carbamazepine. Bias in the estimated effects of dose was also assessed under different simulation scenarios where clearance is a function dose.
520 $a Finally, steady-state PK of phenytoin in epilepsy patients on chronic therapy was estimated using NONMEM. The study design adopted stable isotopes of phenytoin or fosphenytoin administered intravenously or intramuscularly as a replacement of 100mg oral dose. Since the fluctuations at steady-state plasma concentration were observed to be not wide, it was assumed that CL remained constant within each subject and one compartment liner model was applied to fit the PHT data. The half-life (about 42 hours) of phenytoin at steady state and therapeutic levels was found to be longer (almost doubled) than the previously reported values. By modeling the fixed effects of pre-dose concentration of PHT, the parameters which might be inferred as Vmax and Km were also able to be estimated. The legitimacy of the approach should be addressed with simulation studies.
590 $a School code: 0130.
650 4 $a Gerontology. $3 533633
650 4 $a Health Sciences, Pharmacology. $3 1017717
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710 2 0 $a University of Minnesota. $3 676231
773 0 $t Dissertation Abstracts International $g 67-06B.
790 1 0 $a Brundage, Richard C., $e advisor
790 1 0 $a Birnbaum, Angela K., $e advisor
790 $a 0130
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3219968