Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer

G. E. Goodman, Janine G Einspahr, David S Alberts, T. P. Davis, S. A. Leigh, H. S. Chen, F. L. Meyskens

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

13-cis-Retinoic acid (13-CRA) is synthetic analog of vitamin A effective in reversing preneoplastic lesions in both humans and animals. To study its physicochemical properties and disposition kinetics, we developed a rapid, sensitive, and precise high-performance liquid chromatography assay for 13-CRA in biological samples. This assay system resulted in a clear separation of 13-CRA from all-trans-retinoic acid and retinol and had a detection limit of 20 ng/ml plasma. Recovery was 89±6% (S.D.) at equivalent physiological concentrations with a precision of 8%. To study the disposition kinetics in humans, 13 patients received a p.o. bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the first day of 13-CRA administration, the mean time to peak plasma concentration was 222+102 min. Interpatient peak 13-CRA plasma concentrations were found to be variable, suggesting irregular gastrointestinal absorption. β-Phase t 1/2 was approximately 25 hr. The prolonged terminal-phase plasma half-life may represent biliary excretion and enterohepatic circulation.

Original languageEnglish (US)
Pages (from-to)2087-2091
Number of pages5
JournalCancer Research
Volume42
Issue number5
StatePublished - 1982

Fingerprint

Isotretinoin
Pharmacokinetics
Neoplasms
Vitamin A
Enterohepatic Circulation
Tretinoin
Half-Life
Limit of Detection
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goodman, G. E., Einspahr, J. G., Alberts, D. S., Davis, T. P., Leigh, S. A., Chen, H. S., & Meyskens, F. L. (1982). Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer. Cancer Research, 42(5), 2087-2091.

Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer. / Goodman, G. E.; Einspahr, Janine G; Alberts, David S; Davis, T. P.; Leigh, S. A.; Chen, H. S.; Meyskens, F. L.

In: Cancer Research, Vol. 42, No. 5, 1982, p. 2087-2091.

Research output: Contribution to journalArticle

Goodman, GE, Einspahr, JG, Alberts, DS, Davis, TP, Leigh, SA, Chen, HS & Meyskens, FL 1982, 'Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer', Cancer Research, vol. 42, no. 5, pp. 2087-2091.
Goodman, G. E. ; Einspahr, Janine G ; Alberts, David S ; Davis, T. P. ; Leigh, S. A. ; Chen, H. S. ; Meyskens, F. L. / Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer. In: Cancer Research. 1982 ; Vol. 42, No. 5. pp. 2087-2091.
@article{9d04210e8fde4d3b92ce931f9b00753c,
title = "Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer",
abstract = "13-cis-Retinoic acid (13-CRA) is synthetic analog of vitamin A effective in reversing preneoplastic lesions in both humans and animals. To study its physicochemical properties and disposition kinetics, we developed a rapid, sensitive, and precise high-performance liquid chromatography assay for 13-CRA in biological samples. This assay system resulted in a clear separation of 13-CRA from all-trans-retinoic acid and retinol and had a detection limit of 20 ng/ml plasma. Recovery was 89±6{\%} (S.D.) at equivalent physiological concentrations with a precision of 8{\%}. To study the disposition kinetics in humans, 13 patients received a p.o. bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the first day of 13-CRA administration, the mean time to peak plasma concentration was 222+102 min. Interpatient peak 13-CRA plasma concentrations were found to be variable, suggesting irregular gastrointestinal absorption. β-Phase t 1/2 was approximately 25 hr. The prolonged terminal-phase plasma half-life may represent biliary excretion and enterohepatic circulation.",
author = "Goodman, {G. E.} and Einspahr, {Janine G} and Alberts, {David S} and Davis, {T. P.} and Leigh, {S. A.} and Chen, {H. S.} and Meyskens, {F. L.}",
year = "1982",
language = "English (US)",
volume = "42",
pages = "2087--2091",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Pharmacokinetics of 13-cis-retinoic acid in patients with advanced cancer

AU - Goodman, G. E.

AU - Einspahr, Janine G

AU - Alberts, David S

AU - Davis, T. P.

AU - Leigh, S. A.

AU - Chen, H. S.

AU - Meyskens, F. L.

PY - 1982

Y1 - 1982

N2 - 13-cis-Retinoic acid (13-CRA) is synthetic analog of vitamin A effective in reversing preneoplastic lesions in both humans and animals. To study its physicochemical properties and disposition kinetics, we developed a rapid, sensitive, and precise high-performance liquid chromatography assay for 13-CRA in biological samples. This assay system resulted in a clear separation of 13-CRA from all-trans-retinoic acid and retinol and had a detection limit of 20 ng/ml plasma. Recovery was 89±6% (S.D.) at equivalent physiological concentrations with a precision of 8%. To study the disposition kinetics in humans, 13 patients received a p.o. bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the first day of 13-CRA administration, the mean time to peak plasma concentration was 222+102 min. Interpatient peak 13-CRA plasma concentrations were found to be variable, suggesting irregular gastrointestinal absorption. β-Phase t 1/2 was approximately 25 hr. The prolonged terminal-phase plasma half-life may represent biliary excretion and enterohepatic circulation.

AB - 13-cis-Retinoic acid (13-CRA) is synthetic analog of vitamin A effective in reversing preneoplastic lesions in both humans and animals. To study its physicochemical properties and disposition kinetics, we developed a rapid, sensitive, and precise high-performance liquid chromatography assay for 13-CRA in biological samples. This assay system resulted in a clear separation of 13-CRA from all-trans-retinoic acid and retinol and had a detection limit of 20 ng/ml plasma. Recovery was 89±6% (S.D.) at equivalent physiological concentrations with a precision of 8%. To study the disposition kinetics in humans, 13 patients received a p.o. bolus of 13-CRA and had blood samples collected at timed intervals. For the 10 patients studied on the first day of 13-CRA administration, the mean time to peak plasma concentration was 222+102 min. Interpatient peak 13-CRA plasma concentrations were found to be variable, suggesting irregular gastrointestinal absorption. β-Phase t 1/2 was approximately 25 hr. The prolonged terminal-phase plasma half-life may represent biliary excretion and enterohepatic circulation.

UR - http://www.scopus.com/inward/record.url?scp=0020040129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020040129&partnerID=8YFLogxK

M3 - Article

C2 - 7039822

AN - SCOPUS:0020040129

VL - 42

SP - 2087

EP - 2091

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 5

ER -