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PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT).

Record Type:	Electronic resources : Monograph/item
Title/Author:	PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT)./
Author:	HU, OLIVER YOA-PU.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 1984,
Description:	284 p.
Notes:	Source: Dissertations Abstracts International, Volume: 45-07, Section: B.
Contained By:	Dissertations Abstracts International45-07B.
Subject:	Pharmaceuticals. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8429227
ISBN:	9798661957061

PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT).
HU, OLIVER YOA-PU.

PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT). - Ann Arbor : ProQuest Dissertations & Theses, 1984 - 284 p.

Source: Dissertations Abstracts International, Volume: 45-07, Section: B.

Thesis (Ph.D.)--University of Florida, 1984.

This item must not be sold to any third party vendors.

The analytical methods commonly used for assaying phenothiazines in biological fluids were reviewed. Evaluation of the various methods was briefly discussed. A high pressure liquid chromatographic (HPLC) system with ultraviolet light absorption and electrochemical detection methods was developed to permit quantitative determination of a wide range of phenothiazines and some of their metabolites both alone and in combination in various biological fluids. The lower detection limit was approximately 0.1 ng/ml with a 10 ml sample. Simple approaches were developed for the accurate estimation of the extent of drug protein binding with correction for volume shift without measuring volumes directly or indirectly. The underlying assumptions were proved valid by mathematics and computer simulation. These approaches were experimentally applied to the determination of protein binding of promazine (PMZ) and trimeprazine (TMPZ). The error of unbound fraction calculated without correction for volume shift and the magnitude of the volume shift were calculated using derived equations. The stability of PMZ, Nor1PMZ and TMPZ during storage and analysis, and the apparent partition coefficient of TMPZ in hexane-various pH buffer solutions were studied. The kinetics of red blood cell/plasma distribution and distribution coefficient (D), and plasma/cell ratio (P/C) were determined for PMZ and TMPZ. The PMZ plasma data were fitted to two or three compartment models with zero order input for six sets of data. The criteria of computer fitting, and comparisons between first order and zero order input models were discussed. Pharmacokinetic parameters for PMZ were estimated both by computer fitted plasma data, and urinary sigma-minus and rate plots. The bioavailability of TMPZ syrup and two different tablet batches was investigated. Time to the maximum concentration for syrup was significant less than that for one of the tablet batches. The mean relative bioavailability values estimated from AUC(,(INFIN)) for two tablet batches were 69.7% and 71.2% with respect to syrup. Tissue localization of PMZ and Nor1PMZ was studied in rats. Much higher concentrations were found in lung, liver, kidney and brain than in plasma. The PMZ and Nor1PMZ plasma/red blood cell concentration ratio in rats was less than that in humans. This may be an indication that higher brain/plasma concentration ratios are to be expected in humans compared with rats.

ISBN: 9798661957061Subjects--Topical Terms:

3562593
Pharmaceuticals.

PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT).
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100 1 $a HU, OLIVER YOA-PU. $3 3687125
245 1 0 $a PHARMACOKINETIC STUDIES WITH PROMAZINE AND TRIMEPRAZINE (2'-METHYL PROMAZINE) (VOLUME SHIFT).
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 1984
300 $a 284 p.
500 $a Source: Dissertations Abstracts International, Volume: 45-07, Section: B.
500 $a Publisher info.: Dissertation/Thesis.
502 $a Thesis (Ph.D.)--University of Florida, 1984.
506 $a This item must not be sold to any third party vendors.
506 $a This item must not be added to any third party search indexes.
520 $a The analytical methods commonly used for assaying phenothiazines in biological fluids were reviewed. Evaluation of the various methods was briefly discussed. A high pressure liquid chromatographic (HPLC) system with ultraviolet light absorption and electrochemical detection methods was developed to permit quantitative determination of a wide range of phenothiazines and some of their metabolites both alone and in combination in various biological fluids. The lower detection limit was approximately 0.1 ng/ml with a 10 ml sample. Simple approaches were developed for the accurate estimation of the extent of drug protein binding with correction for volume shift without measuring volumes directly or indirectly. The underlying assumptions were proved valid by mathematics and computer simulation. These approaches were experimentally applied to the determination of protein binding of promazine (PMZ) and trimeprazine (TMPZ). The error of unbound fraction calculated without correction for volume shift and the magnitude of the volume shift were calculated using derived equations. The stability of PMZ, Nor1PMZ and TMPZ during storage and analysis, and the apparent partition coefficient of TMPZ in hexane-various pH buffer solutions were studied. The kinetics of red blood cell/plasma distribution and distribution coefficient (D), and plasma/cell ratio (P/C) were determined for PMZ and TMPZ. The PMZ plasma data were fitted to two or three compartment models with zero order input for six sets of data. The criteria of computer fitting, and comparisons between first order and zero order input models were discussed. Pharmacokinetic parameters for PMZ were estimated both by computer fitted plasma data, and urinary sigma-minus and rate plots. The bioavailability of TMPZ syrup and two different tablet batches was investigated. Time to the maximum concentration for syrup was significant less than that for one of the tablet batches. The mean relative bioavailability values estimated from AUC(,(INFIN)) for two tablet batches were 69.7% and 71.2% with respect to syrup. Tissue localization of PMZ and Nor1PMZ was studied in rats. Much higher concentrations were found in lung, liver, kidney and brain than in plasma. The PMZ and Nor1PMZ plasma/red blood cell concentration ratio in rats was less than that in humans. This may be an indication that higher brain/plasma concentration ratios are to be expected in humans compared with rats.
590 $a School code: 0070.
650 4 $a Pharmaceuticals. $3 3562593
650 4 $a Pharmaceutical sciences. $3 3173021
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710 2 $a University of Florida. $3 718949
773 0 $t Dissertations Abstracts International $g 45-07B.
790 $a 0070
791 $a Ph.D.
792 $a 1984
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=8429227