clinical pharmacokinetic

8/2/2019 Clinical Pharmacokinetic

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Click to edit Master subtitle style

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GROUP 8

ZELVI AFIZA(0911011012)RIZKI FEBRIKA PUTRI

(0911012054)ALMUKRAMIN(0911012057)WINDHA WULAN NDARI(0911012074)

Clinical Pharmacokinetic

AMINOPHYLLINE


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Aminophylline

Aminophylline is a 2:1 complex oftheophylline and ethylenediamine.

Theophylline is structurally classified asa methylxanthine. Aminophylline occursas a white or slightly yellowish granuleor powder, with a slight ammoniacalodor. Aminophylline has the chemical

name 1H-Purine-2, 6-dione, 3,7-dihydro-1,3-dimethyl-, compound with 1,2-ethanediamine (2:1). The structuralformula of aminophylline (dihydrate) is

as follows:


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The molecular formula of

aminophylline dihydrate is

C16H24N10O4 2(H2O) with

a molecular weight of 456.46.

Aminophylline Synonymous with

theophylline ethylenediamine,AminophyllinAminophylline AnhydrousAminophylline DihydrateAminophylline Dye Free


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Pharmacology ofAminophylline

A bronchodilator, aminophylline is aderivative of theophylline. Bothaminophylline and theophylline are

methylxanthines and are derived fromthe group called Xanthines. The drugaminophylline differs somewhat in itsstructure from theophylline in that it

contains ethylenediamine, as well asmore molecules of water.Aminophylline tends to be a less

potent and shorter acting than


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Indications

Used as a bronchodilator in reversible airwayobstruction due to asthma. May be used incases of Pulmonary edema and pulmonarycongestion secondary to heart failure. Helpful inrats with pneumonia.

Therapeutic Uses:1. Bronchodilator in reversible airway

obstruction caused by asthma or COPD.

2. Asthma3. COPD

4. Apnea of Prematurity

5. Target serum levels for COPD are 10-12mg/ml


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Mode of Action:

The precise mechanism of action is

unknown. It is thought to be aphosphodiesterase inhibitor which may givea bronchodilatory effect. It also bindsadenosine receptors. Aminophylline may

also increase diaphragm strength andimprove stimulation of the ventilatory drive

Measure of Action:

1. Blood Pressure


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Contraindications:

1. Hypersensitivity to Aminophylline or

Theophylline

2. Cardiac arrhythmias

3. Cigarette smoking is also known to

decresase theophylline levels

. Side effects or precautions:

1. Atrial flutter; Tachycardia

2. Headache; Insomnia; Irritability; Results;Seizures

3. Diarrhea; Nausea; Vomitin


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6. The therapeutic range forTheophylline is less than 20 mg/ml.

Anything over 20mg/ml can havetoxic side effects.

7. >20mg/ml=Nausea

8. >30mg/ml= Cardiac arrhythmias

9. 40-45mg/ml= Seizures

Pharmacodynamics Aminophylline isthe ethylenediamine salt of

theophylline. Theophylline


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Mechanism of action Theophylline isstructurally related to theobromine and

caffeine. The precise mechanism ofaction of theophylline is not known,however, it is thought to be a

phosphodiesterase inhibitor which maygive a bronchodilatory effect. It alsobinds adenosine receptors.

Categories

Phosphodiesterase Inhibitors

Bronchodilator A ents


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Pharmacokinetics Absorption although absorption may

be slow given orally and not aseffective as when given parenterally.

Absorbed orally (given after meals) Metabolized in the liver by Cyt P450enzymes ( t = 8 h )

T is decreased by

Enzyme inducers (phenobarbitone-rifampicin)

T is increased by

Enzyme inhibitor (cimetidine, erythromycin)


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Pharmacokinetics cont.

Protein binding 60%

Half life 7-9 hours

The drug aminophylline differssomewhat in its structure fromtheophylline in that it contains

ethylenediamine, as well as moremolecules of water. Aminophyllinetends to be a less potent and shorteracting than theophylline. They also

cross the placental barrier.


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Clearance

0.29 mL/kg/min [postnatal age 3-15days]

0.64 mL/kg/min [postnatal age 25-57days]

1.7 mL/kg/min [ 1-4 years]

1.6 mL/kg/min [4-12 years]




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Food And Drugs Interactions

Interferon alfa-n1 Interferon increasesthe effect and toxicity of theophylline

Erythromycin The macrolide,

erythromycin, may increase the effectand toxicity of the theophyllinederivative, aminophylline

Ticlopidine Ticlopidine increases theeffect and toxicity of theophylline

Temazepam Aminophylline may

decrease the efficacy of Temazepam.nit r r h n in th th r ti


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Butalbital The barbiturate, butalbital,decreases the effect of aminophylline.

Phenytoin Decreased effect of bothproducts

Pentobarbital The barbiturate,pentobarbital, decreases the effect ofaminophylline.

Sotalol Antagonism of action andincreased effect of theophylline

Cimetidine Cimetidine may increasethe serum concentration ofaminophylline by decreasing its


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Carbamazepine Carbamazepine may

decrease the serum concentration ofaminophylline. Aminophylline maydecrease the serum concentration ofcarbamazepine. Monitor for changes inthe therapeutic effect of both agents ifconcomitant therapy is initiated,discontinued or dose changed.

Propranolol Antagonism of action andincreased effect of theophylline

Adenosine This xanthine decreases theeffect of adenosine


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Food Interactions Limit caffeineintake.

Take with food.

Vitamin B6 needs increased,

supplement recommended.

Doses:

Adult dose for acute asthma: IV:

Loading Dose: 6 mg/kg in 100 to 200

mL of IV fluid intravenously once


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Oral:Loading dose: 6.3 mg/kg orally once.Maintenance Dose: Otherwise healthynonsmoking adult: 12.5 mg/kg/day individed doses. Do not exceed 1,125mg/day.Young adult smoker: 19

mg/kg/day in divided doses.Patientwith cor pulmonale or congestive heartfailure: 6.25 mg/kg/day in divided

doses. Do not exceed 500 mg/day.

Pediatric Dose for Apnea of

Prematurity:


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Pediatric Dose for Acute Asthma:

IV:Loading dose: 6 mg/kg diluted in IVfluid intravenously once over 20 to 30minutes.Maintenance dose: 6 weeks to 6months: 0.5 mg/kg/hour continuousintravenous infusion.6 months to 1

year: 0.6 to 0.7 mg/kg/hr continuousintravenous infusion.1 year to 9 years:1 to 1.2 mg/kg/hr continuous

intravenous infusion.9 years to 12


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Oral:Loading dose: 6.3 mg/kg orally once.Maintenance dose: >=42 < 182days: 12 to 13.5 mg/kg/day individed doses.>= 6 < 12 months: 15

to 22.5 mg/kg/day in divideddoses.>=1 year to =9

years to =12 to=16 years: 6.25 to 20 mg/kg

orally divided every 6 hours.


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Intravenous AdmixtureIncompatibility:

Although there have been reports ofaminophylline precipitating in acidicmedia, these reports do not apply tothe dilute solutions found inintravenous infusions. Aminophyllineinjection should not be mixed in a

syringe with other drugs but shouldbe added separately to theintravenous solution.

When an intravenous solution


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Dose Adjustments

Liver Dose Adjustments

Loading dose: 6 mg/kg (patient notreceiving aminophylline ortheophylline) diluted in IV fluid at arate not more than 25 mg/min.Maintenance dose: 0.25 mg/kg/hr

continuous intravenous infusion. In patients receiving theophylline,

each 0.5 mg/kg theophylline (0.6

mg/kg aminophylline) administered


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Dose Adjustments cont

Dialysis

Aminophylline (theophylline) issomewhat removed with hemodialysis.A 50% supplemental dose oradministering the dose post dialysis isrecommended. A supplemental dose is

not needed with peritoneal dialysis Serum levels may be obtained 15 to

30 minutes following an IV loading

dose

clinical pharmacokinetic

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