Dosage and Pharmacokinetics

The Migraine And Headache Program

Most Effective Migraines Treatments

Get Instant Access

The 10% solution of As2 O3 can be diluted in 250-500 ml of 5% glucose normal solution and administered by intravenous drip for 2-3 h. The standard dosage of 0.16 mg/kg per day over a course of 28-42 days is usually required to induce CR. Importantly, treating APL with low doses of As2O3 (0.08 mg/kg per day) can yield similar CR rate (80%) to that attained with a conventional dosage. In

Table 1 Clinical efficacy and side effects of As203 in APL

Report

Reagent

Disease

m

CR

Time to CR (days)

remission therapy

Survival

Shen

As203

Relapse

15

93.3%

38

Skin (26.7%), GI (26.7%), liver (13.3%),

-

-

et al. 1997

heart (13.3%), leukocytosis (13.3%), headache (6.7%)

Niu

As203

De novo

11

72.7%

35

Leukocytosis (58.6%), liver (37.9%),

As203±

All in CR 8-20

et al. 1999

skin (25.9%), GI (24.1%), heart (15.5%), neuropathy (10.3%)

chemo

(median 12) months

Relapse

47

85.1%

30-39

As20± chemo

2-year DFS41.6%a 2-year OS 50.2%A

Zhang

As203

De novo+

242

74.8%

-

Leukocytosis (75.6%), GI (24.0%),

As203±

5-year OS 92.0%

et al. 2000

relapse+ refractory

skin (22.7%), liver (14.1%)

chemo

7-year OS 76.7%

Soignet

As203

Relapse+

40

85%

35

GI (75%), cough (65%), fatigue (63%),

As203/

18-month

et al. 2001

refractory

fever (63%), headache (60%), heart (55%), leukocytosis (50%), hypokalemia (50%), hyperglycemia (45%), skin (43%), neuropathy (43%), liver (25%), RA syndrome (25%)

OS 66%a

Mathews

As203

De novo

11

91%

52.3

Leukocytosis (63.6%), skin (54.5%), neuro

As203

All in CR 2-33

et al. 2002

pathy (36.4%), fluid retention (27.3%), GI (18.2%), liver (18.2%), RA syndrome (9.1%)

(median 15) months

Table 1 (continued)

Report

Reagent Disease

m

CR

Time to CR (days)

remission therapy

Survival

Au

as2o3 (oral) Relapse

8

100%

37

Liver (38.5%), leukocytosis (30.8%),

Chemo

7 in CR 6-18

et al. 2003

skin (30.8%), headache (15.4%)

(median 14) monthsA

As203+ATRA Relapse

5

80%

31

As203 +

4 in CR 14-19

(oral)

ATRA

(median 17) monthsA

Lazo

As203 Relapse

12

100%

52

Headache (41.7%), skin (33.3%),

As203±

8 in CR 37-181

et al. 2003

fatigue (25.0%), fluid retention (16.7%), GI (16.7%), neuropathy (16.7%)

chemo/ ATRA± chemo

(median 98) weeksA

Raffoux

As203+ATRA Relapse

10

80%

42

Fluid retention (60%), liver (50%), hypoka

As203±

2-year OS 59%A

et al. 2003

lemia (40%), hyperglycemia (30%), heart (30%), leukocytosis (30%), RA syndrome (20%), GI (20%), headache (10%)

ATRA/ HSCT

Shen

As203 De novo

20

90%

31

Leukocytosis (66.7%), liver (55%),

As203 +

2-year DFS 85%

et al. 2004

mouth dryness (11.1%), GI (5.6%), headache (5.6%)

ATRA+ chemo

As203+ATRA De novo

21

95.2%

25.5

Leukocytosis (70%), liver (61.9%), mouth dryness (60%), headache (10%), skin (10%), GI (5%)

2-year DFS 100%

AS2O3, arsenic trioxide; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; CR, complete remission; DFS, disease-free survival; GI, gastrointestinal; HSCT, hematopoietic stem cell transplantation; OS, overall survival; RA, retinoic acid; RFS, relapse-free survival; AAfter relapse

AS2O3, arsenic trioxide; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; CR, complete remission; DFS, disease-free survival; GI, gastrointestinal; HSCT, hematopoietic stem cell transplantation; OS, overall survival; RA, retinoic acid; RFS, relapse-free survival; AAfter relapse the low-dose group, among 14 relapsed patients followed-up for 7-33 months after CR, the estimated disease-free survival (DFS) rates and overall survival (OS) at 2 years were 42±10% and 50±10%, respectively, which were similar to the results obtained among 33 relapsed patients followed up for 7 to 48 months in the standard-dose group (49±15% and 62±16%, respectively; Niu et al. 1999). Hence, low-dose As2O3 treatment was proved equally effective in APL patients, although a larger scale randomized study must be launched in order to reach a firm conclusion (Shen et al. 2001).

Pharmacokinetic studies showed that plasma arsenic concentration rapidly reached the peak level, with the mean Cpmax at 6.85 ^mol/l (5.547.30 ^mol/l), tma 0.89±0.29 h and tmp 12.13±3.31 h (Shen et al. 1997). In patients given 0.08 mg/kg As2O3, the mean Cpmax fell to 2.45 ^mol/l (1.54-2.81 ^mol/l), and the ranges of ti/2a and t1/2p were 1.2-2.7 h (median 1.4h)and6.23-14.9h (median 9.4h), respectively (Shen et al. 2001). Although the mean Cpmax occurred in nearly the half of the results with standard dose, the plasma concentration was maintained in the range of 0.1-0.5 ^mol/l, which is the level of in vitro differentiation.

Urinary arsenic content increased during drug administration, and the total amount of arsenic excreted daily in the urine accounted for 1%-8% of the daily dose. A temporary increase of arsenic in hair and nails was documented, with peak levels at 2.5-2.7 ^g/g tissues, and a decline of arsenic was observed soon after withdrawal of arsenic therapy (Shen et al. 1997).

Was this article helpful?

0 0
The Prevention and Treatment of Headaches

The Prevention and Treatment of Headaches

Are Constant Headaches Making Your Life Stressful? Discover Proven Methods For Eliminating Even The Most Powerful Of Headaches, It’s Easier Than You Think… Stop Chronic Migraine Pain and Tension Headaches From Destroying Your Life… Proven steps anyone can take to overcome even the worst chronic head pain…

Get My Free Audio Book


Post a comment