Pharmacokinetics and acute cardiovascular effects of menogaril in patients with metastatic tumors

A. A. Piergies, Al B Benson III*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 ± 340 l/m2, 38 ± 16 l/h/m2 and 40.3 ± 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 ± 10 / 73.5 ± 8 mmHg) and ejection fractions were in normal range (EF = 68 ± 7%). Transient increase in mean arterial pressure (MAP) from 93 ± 3 to 107 ± 4 mmHg (p ≤ 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 ± 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8% in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 ± 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 ± 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR. The clinical relevance of these observation has to be established.

Original languageEnglish (US)
Pages (from-to)63-69
Number of pages7
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume33
Issue number2
StatePublished - Feb 21 1995

Fingerprint

Menogaril
Pharmacokinetics
Tumors
Neoplasms
Blood pressure
Plasmas
Cardiac Output
Vascular Resistance
Half-Life
Arterial Pressure
Blood Pressure
Doppler Ultrasonography
Cardiac Volume
Hemodynamics
Stroke Volume
Doxorubicin
Colonic Neoplasms
Linear Models
Prostatic Neoplasms
Reference Values

Keywords

  • Anthracyclin
  • Effect
  • Kinetics
  • Menogaril
  • Pharmacokinetics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)

Cite this

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title = "Pharmacokinetics and acute cardiovascular effects of menogaril in patients with metastatic tumors",
abstract = "The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 ± 340 l/m2, 38 ± 16 l/h/m2 and 40.3 ± 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 ± 10 / 73.5 ± 8 mmHg) and ejection fractions were in normal range (EF = 68 ± 7{\%}). Transient increase in mean arterial pressure (MAP) from 93 ± 3 to 107 ± 4 mmHg (p ≤ 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 ± 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8{\%} in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 ± 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 ± 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR. The clinical relevance of these observation has to be established.",
keywords = "Anthracyclin, Effect, Kinetics, Menogaril, Pharmacokinetics",
author = "Piergies, {A. A.} and {Benson III}, {Al B}",
year = "1995",
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T1 - Pharmacokinetics and acute cardiovascular effects of menogaril in patients with metastatic tumors

AU - Piergies, A. A.

AU - Benson III, Al B

PY - 1995/2/21

Y1 - 1995/2/21

N2 - The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 ± 340 l/m2, 38 ± 16 l/h/m2 and 40.3 ± 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 ± 10 / 73.5 ± 8 mmHg) and ejection fractions were in normal range (EF = 68 ± 7%). Transient increase in mean arterial pressure (MAP) from 93 ± 3 to 107 ± 4 mmHg (p ≤ 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 ± 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8% in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 ± 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 ± 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR. The clinical relevance of these observation has to be established.

AB - The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 ± 340 l/m2, 38 ± 16 l/h/m2 and 40.3 ± 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 ± 10 / 73.5 ± 8 mmHg) and ejection fractions were in normal range (EF = 68 ± 7%). Transient increase in mean arterial pressure (MAP) from 93 ± 3 to 107 ± 4 mmHg (p ≤ 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 ± 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8% in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 ± 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 ± 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR. The clinical relevance of these observation has to be established.

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