Online citations, reference lists, and bibliographies.
← Back to Search

Alterations In Tretinoin Pharmacokinetics Following Administration Of Liposomal All-trans Retinoic Acid.

E. Estey, P. Thall, K. Mehta, M. Rosenblum, T. Brewer, V. Simmons, F. Cabanillas, R. Kurzrock, G. López-Berestein
Published 1996 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
We administered liposome-encapsulated all-trans retinoic acid (L-ATRA) to 48 patients with refractory hematologic malignancies using an every-other-day schedule for 28 days and doses of 15 to 175 mg/m2. In 19 patients, pharmacology studies were conducted after the first (day 1) and seventh (day 15) doses. In contrast to the decline in tretinoin concentration seen within 3 to 4 days of administration of daily oral ATRA, there were no differences between the area under the curve (AUC) of tretinoin concentration versus time on day 1 and day 15 (P = .98, Wilcoxon signed-rank test). Peak day 1 concentrations after 15 mg/m2 were higher than those reported after 45 mg/m2 oral ATRA. Six patients with relapsed acute promyelocytic leukemia (APL) were treated. Three, each in first relapse and at least year from the last exposure to oral ATRA, achieved a complete response (CR). Disease recurred in two (one at 3 months despite maintenance L-ATRA and similarity in tretinoin AUC on days 1 and 85, and the other at 5 months, 2 months after discontinuation of L-ATRA) and the third was transplanted 1 month into CR. The three nonresponders were in at least a second relapse and failed to respond to oral ATRA before or immediately after receiving L-ATRA. Severe toxicity developed in three of eight patients treated at 175 mg/m2 (joint pains in two, skin in one). The maximum tolerated dose (MTD) was determined to be 140 mg/m2, at which dose grade 2 toxicity (primarily headache and skin) occurred in eight of eight patients, but grade 3 to 4 toxicity in none. Compared with oral ATRA, L-ATRA apparently results in greater exposure to tretinoin and for a longer time.
This paper references
A Comparison of Some Approximate Confidence Intervals for the Binomial Parameter
B. K. Ghosh (1979)
Retinoid resistance in acute promyelocytic leukemia: new mechanisms, strategies, and implications.
R. Warrell (1993)
Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia.
J. Muindi (1992)
Pharmacokinetics of oral all-trans retinoic acid in patients with acute promyelocytic leukemia.
P. Lefèbvre (1991)
Elevated plasma lipid peroxide content correlates with rapid plasma clearance of all-trans-retinoic acid in patients with advanced cancer.
J. Muindi (1994)
Extra- and intracellular transport of retinoids.
U. Eriksson (1990)
Isotretinoin differs from other synthetic retinoids in its modulation of human cellular retinoic acid binding protein (CRABP)
S. Hirschel-Scholz (1989)
All-trans Retinoic Acid for Acute Promyelocytic Leukemia: Results of the New York Study
S. Frankel (1994)
All trans retinoic acid treatment for patients with acute promyelocytic
P Fenaux (1992)
Pharmacokinetics, tissue distribution, and toxicology of tretinoin incorporated in liposomes
G. López-Berestein (1994)
Resis - tance to all - trans retinoic acid therapy in relapsing acute promyelocytic leukemia : Study of in vitro ATRA sensitivity and cellula retinoic acid binding protein levels in leukemia cells
L Delva (1993)
All-trans retinoic acid: tolerance and biologic effects in myelodysplastic syndrome.
R. Kurzrock (1993)
Retinoid resistance in acute promyelocytic leukemia: new mechanisms, strategies, and implications.
R. Warrell (1993)
Liposomes as drug carriers in cancer therapy.
J. Weinstein (1984)
Induction of differentiation in myeloid leukemia cell lines and acute promyelocytic leukemia cells by liposomal all-trans-retinoic acid.
J. Drach (1993)
Liposome encapsulation circumvents the hepatic clearance mechanisms of all-trans-retinoic acid.
K. Mehta (1994)
All trans retinoic acid treatment for patients with acute promyelocytic leukemia.
P. Fenaux (1992)
Clinical pharmacology of all - rrans retinoic acid in patients with acute promyelocytic leukemia
Muindi JRF (1992)

This paper is referenced by
Enhanced oral bioavailability of all-trans-retinoic acid by 2-hydroxypropyl-β-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique
Z. Chen (2011)
Amphotericin B-incorporated polymeric micelles composed of poly(d,l-lactide-co-glycolide)/dextran graft copolymer.
Kichoon Choi (2008)
Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres.
Y. Choi (2001)
All-trans retinoic acid-incorporated nanoparticles of deoxycholic acid-conjugated dextran for treatment of CT 26 colorectal carcinoma cells
Y. I. Jeong (2013)
In vivo biocompatibility studies of poly(D,L-lactide)/poly(ethylene glycol)-poly(L-lactide) microspheres containing all-trans-retinoic acid
Yongdoo Choi (2002)
Doxorubicin release from self-assembled nanoparticles of deoxycholic acid-conjugated dextran
Y. Jeong (2011)
Phase I trial of interferon α2b and liposome‐encapsulated all‐trans retinoic acid in the treatment of patients with advanced renal cell carcinoma
J. Goldberg (2002)
Biodistribution characteristics of all-trans retinoic acid incorporated in liposomes and polymeric micelles following intravenous administration.
S. Kawakami (2005)
Self-assembled polymeric nanoparticles of poly(ethylene glycol) grafted pullulan acetate as a novel drug carrier
Sun-Woong Jung (2004)
Drug resistance in cancer cells
K. Mehta (2009)
All-trans-retinoic acid release from core-shell type nanoparticles of poly(epsilon-caprolactone)/poly(ethylene glycol) diblock copolymer.
Y. Jeong (2004)
Enhanced dissolution, stability and physicochemical characterization of ATRA/2-hydroxypropyl-β-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique
Zhongming Chen (2013)
Stability and antitumor effects of all-trans retinoic acid-loaded liposomes contained sterylglucoside mixture.
K. Shimizu (2003)
Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro.
Y. Jeong (2010)
Adaptive immunity cooperates with liposomal all-trans-retinoic acid (ATRA) to facilitate long-term molecular remissions in mice with acute promyelocytic leukemia
P. Westervelt (2002)
Antitumor effect of adriamycin-encapsulated nanoparticles of poly(DL-lactide-co-glycolide)-grafted dextran.
K. Choi (2009)
Recent advances in liposome technologies and their applications for systemic gene delivery.
Cullis (1998)
2‐Hydroxypropyl‐β‐cyclodextrin increases aqueous solubility and photostability of all‐trans‐retinoic acid
Lin (2000)
42nd Annual Meeting of American Society of Hematology. San Francisco, CA. December 1-5, 2000.
A. D'Orazio (2001)
Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells
J. Armstrong (2005)
Clinical applications of retinoids in cancer medicine.
L. Camacho (2003)
ESTUDO DA ENCAPSULAÇÃO DA ISOTRETINOÍNA EM LIPOSSOMAS Study of isotretinoin encapsulation into liposomes
C. Pimentel (2007)
Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells
B. Ozpolat (2005)
All-trans retinoic acid-incorporated nanoparticles of deoxycholic acid-conjugated dextran for treatment of CT26 colorectal carcinoma cells
Y. I. Jeong (2013)
All-trans retinoic acid release from surfactant-free nanoparticles of poly(DL-lactide-co-glycolide)
Y. I. Jeong (2008)
Retinoic acid resistance in acute promyelocytic leukemia
R. Gallagher (2002)
New trends in encapsulation of liposoluble vitamins.
M. Gonnet (2010)
Front line clinical trials and minimal residual disease monitoring in acute promyelocytic leukemia.
F. Lococo (2007)
Retinoids and their receptors in cancer development and chemoprevention.
S. Sun (2002)
Liposome-Mediated Delivery of Retinoids
K. Mehta (1998)
Isotretinoin-Containing Liposomes: Obtention, Characterization and In Vitro Cytotoxicity on Leukemia Cells
D. G. Diniz (2008)
Prolonged complete remission in two cases of acute promyelocytic leukaemia treated with atra alone
N. Shehata (2002)
See more
Semantic Scholar Logo Some data provided by SemanticScholar