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Evaluation of the pharmacokinetic-ph...

Learned-Coughlin, Susan M.

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Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers./
Author:	Learned-Coughlin, Susan M.
Description:	571 p.
Notes:	Director: Jurgen Venitz.
Contained By:	Dissertation Abstracts International58-12B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9819509
ISBN:	0591711001

Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers.
Learned-Coughlin, Susan M.

Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers. - 571 p.

Director: Jurgen Venitz.

Thesis (Ph.D.)--Virginia Commonwealth University, 1997.

The goal of this project was to investigate and compare the pharmacokinetics (PK) and pharmacodynamics (PD) of scopolamine in healthy young male and female volunteers, as assessed by peripheral effects on heart rate and saliva flow, as well as central effects on subjective and objective measures of cognitive impairment.

ISBN: 0591711001Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers.
LDR:03911nam 2200301 a 45 001 935843
005 20110510
008 110510s1997 eng d
020 $a 0591711001
035 $a (UnM)AAI9819509
035 $a AAI9819509
040 $a UnM $c UnM
100 1 $a Learned-Coughlin, Susan M. $3 1259546
245 1 0 $a Evaluation of the pharmacokinetic-pharmacodynamic relationship for the central and peripheral effects of scopolamine following intravenous administration to healthy young volunteers.
300 $a 571 p.
500 $a Director: Jurgen Venitz.
500 $a Source: Dissertation Abstracts International, Volume: 58-12, Section: B, page: 6512.
502 $a Thesis (Ph.D.)--Virginia Commonwealth University, 1997.
520 $a The goal of this project was to investigate and compare the pharmacokinetics (PK) and pharmacodynamics (PD) of scopolamine in healthy young male and female volunteers, as assessed by peripheral effects on heart rate and saliva flow, as well as central effects on subjective and objective measures of cognitive impairment.
520 $a The primary objective of this research was to test the following hypotheses: (1) the effect of scopolamine on heart rate is biphasic: low concentrations cause a bradycardic response whereas high concentrations result in a tachycardic effect; (2) scopolamine induces changes in auditory event related potentials (ERP) that can be used as a surrogate measure to assess scopolamine-induced CNS effects as determined by psychometric tests and/or subject-rated sedation scales; (3) PK-PD modeling of scopolamine's PD effects can be used to determine in-vivo EC$\sb{50} $s that can be correlated to muscarinic receptor affinities.
520 $a Results from this study demonstrated that: (1) There was no difference in the PK of scopolamine between male and female subjects. (2) There was a significant gender difference in the central PD measures of scopolamine, with male subjects responding to a greater extent than female subjects. (3) A subset of the male population was identified as being 'hyper-responsive' to the CNS effects of scopolamine. (4) Scopolamine elicited a bi- and tri-phasic effect-time profile on heart rate following bolus and infusion regimens, respectively. (5) Effects on salivary flow were profound, with a $> $9 5% reduction occurring within 30 minutes, regardless of regimen or gender. Salivary flow inhibition peaked at 30-45 minutes, and lasted for approximately 8 hours in all subjects. (6) Subject-rated sedation was similar between genders, peaked at approximately 1.5-2 hours following either bolus or infusion regimens, and lasted for approximately 8-10 hours in most subjects. (7) Scopolamine's effects on P300 latency were profound, and significantly greater in male vs. female study subjects. (8) Correlation analysis revealed no significant relationship between ERP changes and the other CNS PD measures. (9) EC$\sb{50}$ parameters were estimated for each of the 5 PD endpoints by PK-PD modeling; the obtained values may be correlated to muscarinic receptor subtype affinities. The smallest EC$\sb{50}$ (0.05 ng/ml) was estimated for the bradycardic effect of scopolamine on heart rate $\rm(EC\sb{50}\sp{brady}).$ This would indicate that scopolamine-induced cholinomimetic effects are attributable to effects at presynaptic muscarinic M$\sb1$-receptors. The next largest EC$\sb{50}$ (mean (COV%)) of 0.5 ng/ml (75%) was estimated for salivary flow inhibition $\rm(EC\sb{50}\sp{SF}).$ The largest EC$\sb{50}$ (5 ng/ml (75%)) was estimated for the tachycardic effect of scopolamine on heart rate $\rm(EC\sb{50}\sp{tach}).$ (Abstract shortened by UMI.)
590 $a School code: 2383.
650 4 $a Health Sciences, Pharmacology. $3 1017717
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0419
690 $a 0572
710 2 0 $a Virginia Commonwealth University. $3 1018010
773 0 $t Dissertation Abstracts International $g 58-12B.
790 $a 2383
790 1 0 $a Venitz, Jurgen, $e advisor
791 $a Ph.D.
792 $a 1997
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9819509