scholarly journals Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3560-3563
Author(s):  
S Castaigne ◽  
P Lefebvre ◽  
C Chomienne ◽  
E Suc ◽  
F Rigal-Huguet ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
White Blood Cells ◽  
Promyelocytic Leukemia ◽  
Time Curve ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Syndrome

It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.

scholarly journals Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3560-3563 ◽  
Author(s):  
S Castaigne ◽  
P Lefebvre ◽  
C Chomienne ◽  
E Suc ◽  
F Rigal-Huguet ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
White Blood Cells ◽  
Promyelocytic Leukemia ◽  
Time Curve ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Syndrome

Abstract It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.

scholarly journals All-Trans Retinoic Acid–Induced Myositis and Retinoic Acid Syndrome in Microgranular-Variant Acute Promyelocytic Leukemia

2013 ◽  
Vol 44 (4) ◽  
pp. 348-352 ◽  
Author(s):  
Tae-Young Kim ◽  
Chi Hoon Maeng ◽  
Si-Young Kim ◽  
Hwi-Joong Yoon ◽  
Kyung Sam Cho ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Syndrome

The Teratogenic Metabolites of Vitamin A in Women Following Supplements and Liver

1994 ◽  
Vol 13 (1) ◽  
pp. 33-43 ◽  
Author(s):  
N.E. Buss ◽  
E.A. Tembe ◽  
B.D. Prendergast ◽  
A.G. Renwick ◽  
C.F. George
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Retinyl Palmitate ◽  
Time Curve ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Significant Difference ◽  
Oral Supplement

1 Ten healthy female volunteers were given 5 doses of retinol as the palmitate; 50 and 150 mg retinol as an oral supplement, 50 and 150 mg as fried calf liver (50 and 150 g) and 3, 9 or 30 mg by intra-muscular injection. 2 Plasma concentrations of retinyl palmitate were higher after 50 mg retinol given as an oral supplement compared with 50 mg as liver; there was no significant difference between the 150 mg doses. Plasma concentrations of retinol showed only small increases. 3 The peak plasma concentrations (Cmax) of all- trans-retinoic acid, the principal teratogenic metabolite of retinol, and the area under the concentration-time curve (AUC) were up to 20-times higher after supplements compared to the same dose as liver. Plasma concentrations of all- trans-4-oxo-retinoic acid, 13- cis-retinoic acid and 13- cis-4-oxo-retinoic acid showed smaller differences between supplements and liver. 4 Intra-muscular administration of 30 mg retinol gave retinyl palmitate concentrations similar to those found after the oral doses but did not increase circulating concentrations of the acid metabolites. 5 Based on the formation of all- trans-retinoic acid, liver and supplements are not of equivalent teratogenic potential. Advice to pregnant women on the consumption of liver based on the reported teratogenicity of vitamin A supplements should be reconsidered.

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