Pharmacokinetic and Pharmacodynamic Modelling of Arterial Haemodynamic Effects of Terazosin in Healthy Volunteers
Objective: This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the α 1 -adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. Methods: Twenty-four healthy volunteers...
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| Published in | Clinical drug investigation Vol. 28; no. 3; pp. 139 - 147 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Cham
Springer International Publishing
01.01.2008
Wolters Kluwer Health, Inc |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1173-2563 1179-1918 |
| DOI | 10.2165/00044011-200828030-00001 |
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| Abstract | Objective:
This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the α
1
-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg.
Methods:
Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E
max
) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated.
Results:
For systolic blood pressure, Emax was 29.9 ± 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 ± 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E
max
effect compartment model. The obtained first-order rate constant values (0.40 ± 0.006 h
−l
for systolic blood pressure and 0.47 ± 0.012 h
−l
for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC50 (concentration of terazosin that induces an effect at 50% of E
max
values) values were similar for systolic (29.9 ± 4.3 μg/L) and diastolic (28.7 ± 4.0 μg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin.
Conclusion:
The direct haemodynamic effects of terazosin can be characterized by an Emax effect compartment model. |
|---|---|
| AbstractList | Objective: This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the [α.sub.1]-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. Methods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease ([E.sub.max]) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated. Results: For systolic blood pressure, [E.sub.max] was 29.9 ± 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 ± 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory [E.sub.max] effect compartment model. The obtained first-order rate constant values (0.40 ± 0.006 [h.sup.-1] for systolic blood pressure and 0.47 ± 0.012 [h.sup.-1] for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. [EC.sub.50] (concentration of terazosin that induces an effect at 50% of [E.sub.max] values) values were similar for systolic (29.9 ± 4.3 µg/L) and diastolic (28.7 ± 4.0 µg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin. Conclusion: The direct haemodynamic effects of terazosin can be characterized by an [E.sub.max] effect compartment model. This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the alpha(1)-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. M ethods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E(max)) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated.OBJECTIVEThis study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the alpha(1)-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. M ethods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E(max)) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated.For systolic blood pressure, E(max) was 29.9 +/- 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 +/- 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E(max) effect compartment model. The obtained first-order rate constant values (0.40 +/- 0.006 h(-)(1) for systolic blood pressure and 0.47 +/- 0.012 h(-)(1) for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC(50) (concentration of terazosin that induces an effect at 50% of E(max) values) values were similar for systolic (29.9 +/- 4.3 microg/L) and diastolic (28.7 +/- 4.0 microg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin.RESULTSFor systolic blood pressure, E(max) was 29.9 +/- 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 +/- 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E(max) effect compartment model. The obtained first-order rate constant values (0.40 +/- 0.006 h(-)(1) for systolic blood pressure and 0.47 +/- 0.012 h(-)(1) for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC(50) (concentration of terazosin that induces an effect at 50% of E(max) values) values were similar for systolic (29.9 +/- 4.3 microg/L) and diastolic (28.7 +/- 4.0 microg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin.The direct haemodynamic effects of terazosin can be characterized by an E(max) effect compartment model.CONCLUSIONThe direct haemodynamic effects of terazosin can be characterized by an E(max) effect compartment model. This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the alpha(1)-adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. M ethods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E(max)) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated. For systolic blood pressure, E(max) was 29.9 +/- 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 +/- 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E(max) effect compartment model. The obtained first-order rate constant values (0.40 +/- 0.006 h(-)(1) for systolic blood pressure and 0.47 +/- 0.012 h(-)(1) for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC(50) (concentration of terazosin that induces an effect at 50% of E(max) values) values were similar for systolic (29.9 +/- 4.3 microg/L) and diastolic (28.7 +/- 4.0 microg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin. The direct haemodynamic effects of terazosin can be characterized by an E(max) effect compartment model. Objective: This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the α 1 -adrenoceptor antagonist terazosin and its effects on arterial blood pressure after a single oral administration of terazosin 2 mg. Methods: Twenty-four healthy volunteers participated in this study. Pharmacokinetic and pharmacodynamic modeling were performed subject by subject. First, plasma concentrations were fitted according to a one-compartment model with first-order absorption and monoexponential elimination. Then the maximum drug-induced decrease (E max ) effect compartment-model was developed to describe the pharmacodynamic relationships between systolic and diastolic blood pressure and plasma concentrations using the pharmacokinetic parameters that were previously estimated. Results: For systolic blood pressure, Emax was 29.9 ± 10.6 mmHg. The corresponding value for decrease in diastolic blood pressure was 39.7 ± 8.6 mmHg. The effects of terazosin on systolic and diastolic blood pressure could be quantified by an inhibitory E max effect compartment model. The obtained first-order rate constant values (0.40 ± 0.006 h −l for systolic blood pressure and 0.47 ± 0.012 h −l for diastolic blood pressure) were consistent with the rapid development of pharmacological effect. EC50 (concentration of terazosin that induces an effect at 50% of E max values) values were similar for systolic (29.9 ± 4.3 μg/L) and diastolic (28.7 ± 4.0 μg/L) blood pressure. A decrease in diastolic blood pressure was the most sensitive response after oral administration of a single dose of terazosin. Conclusion: The direct haemodynamic effects of terazosin can be characterized by an Emax effect compartment model. |
| Audience | Academic |
| Author | Azanza, Jose Ramón Campanero, Miguel Angel Sádaba, Belén Muñoz- Juarez, Maria José Quetglas, Emilio García |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18266399$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.2165/00003088-198917040-00004 10.2165/00002512-199303030-00007 10.2165/00003495-198733050-00003 10.3999/jscpt.14.147 10.1016/0002-8703(91)90808-U 10.1016/0002-9343(86)90847-8 10.1046/j.1464-410X.1998.00747.x 10.1016/0002-8703(91)90810-5 10.3999/jscpt.13.137 10.1016/S0009-9236(98)90053-4 10.1016/0300-2977(94)00057-G 10.1002/j.1552-4604.1996.tb04172.x 10.1177/009127000004001011 10.1002/j.1552-4604.1998.tb05793.x 10.1159/000475055 |
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| Keywords | Prazosin Terazosin Pharmacodynamic Parameter Systolic Blood Pressure Diastolic Blood Pressure |
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This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the α
1
-adrenoceptor antagonist... This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the alpha(1)-adrenoceptor antagonist terazosin... Objective: This study aimed to investigate, in healthy volunteers, the relationship between the plasma concentrations of the [α.sub.1]-adrenoceptor antagonist... |
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| SubjectTerms | Abdominal Pain - chemically induced Administration, Oral Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists - administration & dosage Adrenergic alpha-Antagonists - pharmacokinetics Adrenergic alpha-Antagonists - pharmacology Adult Algorithms Area Under Curve Blood Pressure - drug effects Chromatography, High Pressure Liquid Dizziness - chemically induced Dose-Response Relationship, Drug Female Half-Life Headache - chemically induced Heart Rate - drug effects Humans Internal Medicine Male Medicine Medicine & Public Health Original Research Article Pharmacology/Toxicology Pharmacotherapy Prazosin - analogs & derivatives Prazosin - blood Prazosin - pharmacokinetics Prazosin - pharmacology Tachycardia - chemically induced Time Factors |
| Title | Pharmacokinetic and Pharmacodynamic Modelling of Arterial Haemodynamic Effects of Terazosin in Healthy Volunteers |
| URI | https://link.springer.com/article/10.2165/00044011-200828030-00001 https://www.ncbi.nlm.nih.gov/pubmed/18266399 https://www.proquest.com/docview/70281158 |
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