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Zero order release

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Zero order release

cmlingam78
This post was updated on .
Ropinirole HCL

Time Predicted
0 0.00
1 10.08
2 17.96
3 24.00
4 28.51
5 31.74
6 33.94
7 35.28
8 35.92
9 36.00
10 35.64
12 33.94
16 28.51
24 16.98
36 6.37
48 2.12

Nisoldipine:

Time Predicted
0 0.00
1 22.01
2 41.05
3 57.41
4 71.37
5 83.18
6 93.07
7 101.24
8 107.89
9 113.17
10 117.24
12 122.31
16 123.25
24 105.60
36 68.38
48 39.36

Carvedilol:

Time (hr) Predicted
0 0.0
1 630.9
2 1168.3
3 1622.6
4 2003.1
5 2318.3
6 2575.8
7 2782.4
8 2944.3
9 3066.8
10 3155.0
12 3245.7
16 3180.4
24 2576.6
36 1534.1
48 811.9

Ivabradine:

Cmax: app. 250 ng/ml
Tmax: 6 hours

VBP
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Ropinirole Biopharmaceutical Charecters

VBP

Ropinirole is an orally administered non-ergoline dopamine agonist used for the treatment of Idiopathic Parkinson’s disease. The below mentioned Biopharmaceutical Charecters may be useful for you.

4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one monohydrochloride

Properties

Description

Appearance

White to yellow solid

Molecular formula

C16H24N2O•HCl

Molecular Mass

296.84 (260.38 as the free base)

Category

non-ergoline dopamine agonist

Use

Ttreatment of the signs and symptoms of idiopathic Parkinson’s disease.

Solubility

133 mg/mL in water.

Melting Point

243° to 250°C

BCS Class

Class I

Log P

3.16

Pka

15.55

Protein Binding

40%

Bio availability

55% ( First pass metabolism)

Metabolism

Extensively metabolized by the liver, N-despropylation and hydroxylation to form the inactive N-despropyl and hydroxy metabolites.

Vd

7.5 L/kg

T ½

6 hours.

T max

1-2 hours.

Dosing

1 to 8 mg 3 times daily.

Route of elimination

urine.

Strength

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, or 5 mg(IR).

2 mg, 4 mg, 6 mg, 8 mg, and 12 mg(XR)

Available Marketed products

Requip Tiltab(Glaxo) Tablets ,REQUIP XL tablets

Mechanism of Action:

Ropinirole HCl is a non-ergoline dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4 receptor subtypes

Absorption

Ropinirole is rapidly absorbed after oral administration, reaching peak concentration in approximately 1-2 hours. In clinical studies, over 88% of a radio labelled dose was recovered in urine and the absolute bioavailability was 55%, indicating a first-pass effect. Relative bioavailability from a tablet compared to an oral solution is 85%. Food does not affect the extent of absorption of ropinirole, although its Tmax is increased by 2.5 hours and its Cmax is decreased by approximately 25% when the drug is taken with a high-fat meal. The clearance of ropinirole after oral administration to patients is 47 L/hr (cv = 45%) and its elimination half-life is approximately 6 hours.

Metabolism

Ropinirole is extensively metabolized by the liver to inactive metabolites and displays linear kinetics over the therapeutic dosing range of 1 to 8 mg 3 times daily. Steady-state concentrations are expected to be achieved within 2 days of dosing. The major metabolic pathways are N-despropylation and hydroxylation to form the inactive N-despropyl and hydroxy metabolites.

Distribution

Ropinirole is widely distributed throughout the body, with an apparent volume of distribution of 7.5 L/kg (cv = 32%). It is up to 40% bound to plasma proteins and has a blood-to-plasma ratio of 1:1.

Excretion

Less than 10% of the administered dose is excreted as unchanged drug in urine. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

VBP
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Re: Zero order release

VBP
In reply to this post by cmlingam78

Ivabradine HCl is used for the symptomatic treatment of chronic stable angina pectoris patients with normal sinus rhythm, commonly used when Contraindication or intolerance to beta blockers. Ivabradine HCl is a pure heart rate lowering agent having selective and specific inhibition of the cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node. . The below mentioned Biopharmaceutical Charecters may be useful for you.

Properties

Description

Appearance

White to slightly yellow powder

Molecular formula

C 27 H 35 N2 O5

Molecular Mass

468.585 g/mol

Category

Anti ischemic drug

Use

Chronic stable angina Pectoris

solubility

Highly soluble ( > 10 mg / ml)

Melting Point

193 – 196 o C

BCS Class

Class I

Log P

2.71

Protein Binding

70 -75 %

Bio availability

40 %

Metabolism

Hepatic ( Cytochrome CYP 3 A4)

Vd

100 L

T ½

2 hrs

T max

1 hr

Dosing

Bid ( 5 mg Twice daily, increased up to 7.5 mg twice daily after 3-4 weeks)

Route of elimination

Faceus and urine

Strength

5, 7.5 mg tablets

Available products

Ivabrad (Lupin) Ivabrid ( Piramal), Procoralan ( Servier) Coralan ( Servier)

Mechanism of Action And Pharmacological Effects

It blocks If channels (f-funny) which is responsible for spontaneous diastolic depolarisation of Sino Atrial node. This block reduces the heart rate resulting in decreased myocardial oxygen demand, thus improving the clinical situation. It can be used as an alternative in patients with intolerance or contraindication to beta blockers. The most prevalent cardiovascular disease is the coronary artery obstruction which decreases the myocardial oxygen supply causing ischemia of the myocardium. The coronary blood flow occurs during the diastole, so decreasing the heart rate allows more time for left ventricular filling and coronary perfusion, and thus maintains the oxygen balance. Tachycardia decreases duration of diastole, accelerates atherosclerosis , disrupts the coronary plaques and increases the occurrence of sudden cardiac death.[1] In angina, beta blockers and calcium channel blockers are used to decrease heart rate, but they are associated with adverse effects like hypotension, negative inotropism, bradycardia and AV conduction disturbances, reflex tachycardia and peripheral edema.[1] In view of this, a novel heart rate lowering drug, ivabradine with an activity on the sinoatrial (SA) node, can be used.

Absorption

Ivabradine is rapidly and almost completely absorbed after oral administration with a peak plasma level reached in about 1 hour under fasting condition. Food delays the absorption by 1 hour and increased plasma exposure by 20 to 30 %. Peak plasma concentration is attained after 45-90 minutes and steady state concentration (10ng/ml) is achieved within 1 day. On oral administration, 90% gets absorbed with absolute bioavailability around 40%, due to first-pass effect in the gut and liver. The intake of the tablet during meals is recommended in order to decrease intra-individual variability in exposure.

Distribution

Ivabradine is approximately 70% plasma protein bound and the volume of distribution at steady-state is close to 100 l in patients. The maximum plasma concentration following chronic administration at the recommended dose of 5 mg twice daily is 22 ng/ml The average plasma concentration is 10 ng/ml at steady-state. The half life is 2 hours.

Metabolism

It undergoes metabolism by oxidation and hydroxylation involving cytochrome (CYP) 3A4

only. The N-desmethylated metabolite S18982 is active, contributing to pharmacological effect and 70-75% is bound to plasma proteins. It is also metabolised by CYP3A4 with same half life.

Elimination

Ivabradine is eliminated with a main half-life of 2 hours (70-75% of the AUC) in plasma and an effective half-life of 11 hours. The total clearance is about 400 ml/min and the renal clearance is about 70 ml/min. Excretion of metabolites occurs to a similar extent via faeces and urine..

Linearity/non linearity

The kinetics of ivabradine is linear over an oral dose range of 0.5 – 24 mg.

VBP
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Re: Zero order release

VBP
@ cmlingam

Find attached fileRopi_&_Iva.txt
VBP
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Re: Zero order release

VBP
In reply to this post by cmlingam78
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Ropinirole:

Parameter

Units

Estimate

AUC

hr*ng/mL

207.79221

K_HL

hr

6.0012743

CL_F

mL/hr

57750

Tmax

hr

8.6580087

Cmax

ng/mL

8.8291066


Ropinirole:

Time_obs (hr)

Time (hr)

Predicted (ng/mL)

0

0

0

1

1

2.4696318

2

2

4.4004916

3

3

5.8807327

4

4

6.9856877

5

5

7.7796161

6

6

8.317224

7

7

8.6449837

8

8

8.8022786

9

9

8.8223975

10

10

8.7333949

12

12

8.3184483

16

16

6.9877443

24

24

4.1604486

36

36

1.5606276

48

48

0.52036234

IVA:

Parameter

Units

Estimate

AUC

hr*ng/mL

102.1201

K_HL

hr

2.0004248

CL_F

mL/hr

99099

Tmax

hr

2.8860029

Cmax

ng/mL

13.017273


IVA

Time_obs (hr)

Time (hr)

Predicted (ng/mL)

0

0

0

1

1

8.6703111

2

2

12.262574

3

3

13.007381

4

4

12.264379

5

5

10.84108

6

6

9.1996381

7

7

7.5898727

8

8

6.1339948

9

9

4.8799221

10

10

3.834311

12

12

2.3009252

16

16

0.76720088

24

24

0.071967439

36

36

0.001688227

48

48

3.520247E-05


NISO:

Parameter

Units

Estimate

AUC

hr*ng/mL

20935.961

K_HL

hr

9.9021026

CL_F

mL/hr

406

Tmax

hr

14.285714

Cmax

ng/mL

539.13366

NISO:

Time_obs (hr)

Time (hr)

Predicted (ng/mL)

0

0

0

1

1

95.650745

2

2

178.36833

3

3

249.46429

4

4

310.13195

5

5

361.45639

6

6

404.42365

7

7

439.92913

8

8

468.78537

9

9

491.72915

10

10

509.42803

12

12

531.45054

16

16

535.5489

24

24

458.86558

36

36

297.14565

48

48

171.04121


Carve:

Parameter

Units

Estimate

AUC

hr*ng/mL

114929.32

K_HL

hr

9.0019114

CL_F

mL/hr

87.01

Tmax

hr

12.987013

Cmax

ng/mL

3255.5703

Carve:

Time_obs (hr)

Time (hr)

Predicted (ng/mL)

0

0

0

1

1

630.91609

2

2

1168.3176

3

3

1622.6001

4

4

2003.132

5

5

2318.3495

6

6

2575.8435

7

7

2782.4386

8

8

2944.2648

9

9

3066.823

10

10

3155.0448

12

12

3245.678

16

16

3180.3979

24

24

2576.6019

36

36

1534.0887

48

48

811.89733

VBP
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Re: Zero order release

VBP
This post was updated on .
In reply to this post by cmlingam78

Formulation

Tlag

Tmax

Cmax

AUClast

AUCINF_obs

HL_Lambda_z

Carvedilol

0.00

12.00

3245.70

101711.10

118583.96

14.40

Iva

0.00

6.00

99.28

689.91

690.47

2.00

Nisoldipine

0.00

16.00

123.25

4085.40

5042.57

16.86

Ropinirole

0.00

9.00

36.00

838.73

863.18

8.00

VBP
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Re: Zero order release

VBP
In reply to this post by cmlingam78
IVA

0 0
1 33.227746
2 56.725039
3 73.341358
4 85.091734
5 93.401116
6 99.277169
7 70.204725
8 49.645891
9 35.107529
10 24.826599
12 12.415127
16 3.1046954
24 0.1941577
36 0.0030363
48 0.0000000
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