Geodon (Ziprasidone) is an antipsychotic used to treat schizophrenia and riot bipolar. Uses, proportion, side effects of Geodon.
Monday, January 4, 2010
Geodon Generic
Geodon (Ziprasidone) is an antipsychotic used to treat schizophrenia and riot bipolar. Uses, proportion, side effects of Geodon.
Clinical Pharmacology 4
Special Populations
The age and the Effects of Sex - In the numerous dose (8 days of treatment) the study implicating 32 subjects, there was no difference in the pharmacokinetics of ziprasidone between the men and the women or between the rather old (> 65 years old) and young person (18 - 45 years) subjects. Supplémentairement, the pharmacokinetic population the valuation of patients in controlled trials revealed no obviousness of clinically significant age or of difference linked by sex in the pharmacokinetics of ziprasidone. The modifications of proportion for age or sex are not recommended, therefore.
Intramuscular Ziprasidone was not systematically assessed in the rather old patients (65 years and over).
Running - No study of specific pharmacokinetic was driven to investigate the effects of running. The pharmacokinetic population valuation revealed no obviousness of difference linked by running clinically significant in the pharmacokinetics of ziprasidone. The modifications of proportion for running are not recommended, therefore.
By smoking - Founded on in studies of vitro using human enzymes of liver, ziprasidone a substrate for CYP1A2 is not; tobacco addiction should therefore have no effect on the pharmacokinetics of ziprasidone. In harmony with these in results of vitro, the population pharmacokinetic valuation did not reveal difference pharmacokinetic significant between the smokers and the nonsmokers.
The Renal Weakening - since ziprasidone is highly transformed by metabolism, with less than 1 % medicaments excreted the only unchanged, renal weakening will not have probably impact mattering on the pharmacokinetics of ziprasidone. The pharmacokinetics of ziprasidone further to 8 days of proportion of OFFER of 20 mgs was similar among subjects with the variable levels of renal weakening (n=27) and subjects with normal renal function, by pointing out that the adaptation of proportion based on the level of renal weakening is not demanded. Ziprasidone is not taken away by hemodialysis.
The Hepatic Weakening - As ziprasidone are considerably cleared by the liver, they would expect that in the presence of hepatic weakening augments AUC of ziprasidone; a study of the numerous dose in the OFFER of 20 mgs for 5 days in subjects (n=13) with clinically significant (the Class A Childs-Pugh and B) the cirrhosis revealed an increase in AUC 0-12 of 13 % and of 34 % in the Class A Childs-Pugh and B, respectively, compared with a group of corresponded control (N=14). A half-life of 7.1 hours was noticed in subjects with the cirrhosis compared at 4.8 am in the group of control.
Intramuscular Ziprasidone was not systematically assessed in the rather old patients or in the patients with the hepatic or renal weakening. As the cyclodextrin excipient is clear by renal filtering, ziprasidone intramuscular should be managed with caution to the patients with weak renal function.
Reciprocal actions of medicament of the Medicament
One in the study of inhibition of enzyme vitro using the human liver microsomes showed that ziprasidone had not enough inhibitive effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 and would not interfere probably so the metabolism of medicaments principally transformed by metabolism by these enzymes. In vivo studies revealed no effect of ziprasidone on the pharmacokinetics of dextromethorphan, oestrogen, progesterone, or lithium.
In vivo studies revealed that a reduction about 35 % in ziprasidone AUC by concomitantly managed carbamazepine, an increase about 35-40 % in ziprasidone AUC by concomitantly managed ketoconazole, but any effect on the pharmacokinetics of ziprasidone by cimetidine or antiacid.
The age and the Effects of Sex - In the numerous dose (8 days of treatment) the study implicating 32 subjects, there was no difference in the pharmacokinetics of ziprasidone between the men and the women or between the rather old (> 65 years old) and young person (18 - 45 years) subjects. Supplémentairement, the pharmacokinetic population the valuation of patients in controlled trials revealed no obviousness of clinically significant age or of difference linked by sex in the pharmacokinetics of ziprasidone. The modifications of proportion for age or sex are not recommended, therefore.
Intramuscular Ziprasidone was not systematically assessed in the rather old patients (65 years and over).
Running - No study of specific pharmacokinetic was driven to investigate the effects of running. The pharmacokinetic population valuation revealed no obviousness of difference linked by running clinically significant in the pharmacokinetics of ziprasidone. The modifications of proportion for running are not recommended, therefore.
By smoking - Founded on in studies of vitro using human enzymes of liver, ziprasidone a substrate for CYP1A2 is not; tobacco addiction should therefore have no effect on the pharmacokinetics of ziprasidone. In harmony with these in results of vitro, the population pharmacokinetic valuation did not reveal difference pharmacokinetic significant between the smokers and the nonsmokers.
The Renal Weakening - since ziprasidone is highly transformed by metabolism, with less than 1 % medicaments excreted the only unchanged, renal weakening will not have probably impact mattering on the pharmacokinetics of ziprasidone. The pharmacokinetics of ziprasidone further to 8 days of proportion of OFFER of 20 mgs was similar among subjects with the variable levels of renal weakening (n=27) and subjects with normal renal function, by pointing out that the adaptation of proportion based on the level of renal weakening is not demanded. Ziprasidone is not taken away by hemodialysis.
The Hepatic Weakening - As ziprasidone are considerably cleared by the liver, they would expect that in the presence of hepatic weakening augments AUC of ziprasidone; a study of the numerous dose in the OFFER of 20 mgs for 5 days in subjects (n=13) with clinically significant (the Class A Childs-Pugh and B) the cirrhosis revealed an increase in AUC 0-12 of 13 % and of 34 % in the Class A Childs-Pugh and B, respectively, compared with a group of corresponded control (N=14). A half-life of 7.1 hours was noticed in subjects with the cirrhosis compared at 4.8 am in the group of control.
Intramuscular Ziprasidone was not systematically assessed in the rather old patients or in the patients with the hepatic or renal weakening. As the cyclodextrin excipient is clear by renal filtering, ziprasidone intramuscular should be managed with caution to the patients with weak renal function.
Reciprocal actions of medicament of the Medicament
One in the study of inhibition of enzyme vitro using the human liver microsomes showed that ziprasidone had not enough inhibitive effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 and would not interfere probably so the metabolism of medicaments principally transformed by metabolism by these enzymes. In vivo studies revealed no effect of ziprasidone on the pharmacokinetics of dextromethorphan, oestrogen, progesterone, or lithium.
In vivo studies revealed that a reduction about 35 % in ziprasidone AUC by concomitantly managed carbamazepine, an increase about 35-40 % in ziprasidone AUC by concomitantly managed ketoconazole, but any effect on the pharmacokinetics of ziprasidone by cimetidine or antiacid.
Clinical Pharmacology 3
Metabolism and Elimination: Ziprasidone is copiously transformed by metabolism after the oral administration with only a small quantity excreted in the urine (<1 style="font-weight: bold;">Intramuscular Pharmacokinetics Systemic
Bioavailability: the bioavailability of ziprasidone constituent is intramusculairement 100 %. After the intramuscular administration of simple doses, maximum concentration of serum occurs typically in about post dose 60 minutes or earlier and medium half-life (T ½) vary from two to five hours. The increase of exhibition in a way linked by the dose and further to three days of intramuscular proportion, not enough accumulation is noticed.
Metabolism and Elimination: Although the metabolism and the elimination of IM ZIPRASIDONE are not systematically assessed, they would not expect what in the intramuscular road of administration change the tracks of the metabolism.
Bioavailability: the bioavailability of ziprasidone constituent is intramusculairement 100 %. After the intramuscular administration of simple doses, maximum concentration of serum occurs typically in about post dose 60 minutes or earlier and medium half-life (T ½) vary from two to five hours. The increase of exhibition in a way linked by the dose and further to three days of intramuscular proportion, not enough accumulation is noticed.
Metabolism and Elimination: Although the metabolism and the elimination of IM ZIPRASIDONE are not systematically assessed, they would not expect what in the intramuscular road of administration change the tracks of the metabolism.
Clinical Pharmacology 2
Oral Pharmacokinetics
The activity of Ziprasidone is principally because of parental medicament. Numerous dose pharmacokinetics of ziprasidone is proportional of the dose in the range of offered clinical dose and ziprasidone accumulation is foreseeable with numerous proportion. The elimination of ziprasidone is mainly via the hepatic metabolism with a medium final half-life about 7 hours in the range of offered clinical dose. Permanent concentration is fulfilled in the course of one-three days of proportion. The medium visible systematic permission is 7.5 millilitres / minutes / kg. Ziprasidone will not interfere probably the metabolism of medicaments transformed by metabolism by cytochrome P450 enzymes.
Absorption: Ziprasidone is well-absorbed after the oral administration, by attaining maximum plasma concentration in 6 - 8 hours. Bioavailability absolute of a dose of 20 mgs under fed conditions is 60 %. The absorption of ziprasidone is augmented up to double in the presence of the food.
Distribution: Ziprasidone has a medium visible volume of distribution of 1.5 L / kg. It is bigger than 99 % tied to plasma proteins, by making friends principally in the albumin and in the glycoprotein α1-acid. In the vitro plasma protein making friends of ziprasidone was not changed by warfarin or propranolol, two highly proteinbound medicaments, ziprasidone either changed fact to make friends of these medicaments in plasma human being. So, the potential for the reciprocal actions of medicament with ziprasidone because of displacement is minimal.
The activity of Ziprasidone is principally because of parental medicament. Numerous dose pharmacokinetics of ziprasidone is proportional of the dose in the range of offered clinical dose and ziprasidone accumulation is foreseeable with numerous proportion. The elimination of ziprasidone is mainly via the hepatic metabolism with a medium final half-life about 7 hours in the range of offered clinical dose. Permanent concentration is fulfilled in the course of one-three days of proportion. The medium visible systematic permission is 7.5 millilitres / minutes / kg. Ziprasidone will not interfere probably the metabolism of medicaments transformed by metabolism by cytochrome P450 enzymes.
Absorption: Ziprasidone is well-absorbed after the oral administration, by attaining maximum plasma concentration in 6 - 8 hours. Bioavailability absolute of a dose of 20 mgs under fed conditions is 60 %. The absorption of ziprasidone is augmented up to double in the presence of the food.
Distribution: Ziprasidone has a medium visible volume of distribution of 1.5 L / kg. It is bigger than 99 % tied to plasma proteins, by making friends principally in the albumin and in the glycoprotein α1-acid. In the vitro plasma protein making friends of ziprasidone was not changed by warfarin or propranolol, two highly proteinbound medicaments, ziprasidone either changed fact to make friends of these medicaments in plasma human being. So, the potential for the reciprocal actions of medicament with ziprasidone because of displacement is minimal.
Clinical Pharmacology 1
Pharmacodynamics
Ziprasidone displayed high in vitro the affinity making friends for the dopamine D2 and D3, the serotonin 5HT2A, 5HT2C, 5HT1A, 5HT1D and receivers 1-adrenergic (Ki s of 4.8, 7.2, 0.4, 1.3, 3.4, 2 and 10 nM, respectively) and the affinity softened for the histamine H1's receiver (Ki=47 nM). Ziprasidone worked as an antagonistic in the D2, 5HT2A and 5HT1D receivers and as an agonist in the 5HT1A the receiver. Ziprasidone inhibited the reconsommation synaptic of serotonin and of norepinephrine. No significant affinity was displayed for other sites of récepteur/attacher assessed, by including the cholinergic muscarinic the receiver (IC50> 1 M).
The mechanism of action of ziprasidone, as with other medicaments having effectiveness in schizophrenia, is unknown. However, they offered that the effectiveness of this medicament in schizophrenia is negotiated by a combination of type of dopamine 2 (D2) and serotonin type 2 (5HT2) antagonism. As with other medicaments having effectiveness in riot bipolar, the mechanism of action of ziprasidone in riot bipolar am unknown.
The antagonism in receivers other than dopamine and 5HT2 with the similar affinity of receiver can explain a little other therapeutics and side effects of ziprasidone. The antagonism of Ziprasidone of histamine H1's receivers can explain the drowsiness noticed with this medicament. The antagonism of adrénergiques Ziprasidone of α1-receivers can explain the orthostatic low blood pressure noticed with this medicament.
Ziprasidone displayed high in vitro the affinity making friends for the dopamine D2 and D3, the serotonin 5HT2A, 5HT2C, 5HT1A, 5HT1D and receivers 1-adrenergic (Ki s of 4.8, 7.2, 0.4, 1.3, 3.4, 2 and 10 nM, respectively) and the affinity softened for the histamine H1's receiver (Ki=47 nM). Ziprasidone worked as an antagonistic in the D2, 5HT2A and 5HT1D receivers and as an agonist in the 5HT1A the receiver. Ziprasidone inhibited the reconsommation synaptic of serotonin and of norepinephrine. No significant affinity was displayed for other sites of récepteur/attacher assessed, by including the cholinergic muscarinic the receiver (IC50> 1 M).
The mechanism of action of ziprasidone, as with other medicaments having effectiveness in schizophrenia, is unknown. However, they offered that the effectiveness of this medicament in schizophrenia is negotiated by a combination of type of dopamine 2 (D2) and serotonin type 2 (5HT2) antagonism. As with other medicaments having effectiveness in riot bipolar, the mechanism of action of ziprasidone in riot bipolar am unknown.
The antagonism in receivers other than dopamine and 5HT2 with the similar affinity of receiver can explain a little other therapeutics and side effects of ziprasidone. The antagonism of Ziprasidone of histamine H1's receivers can explain the drowsiness noticed with this medicament. The antagonism of adrénergiques Ziprasidone of α1-receivers can explain the orthostatic low blood pressure noticed with this medicament.
Description
GEODON is available as the Capsules of GEODON (ziprasidone the hydrochloride) for the oral administration and as GEODON for the Injection (ziprasidone mesylate) for intramuscular injection. Ziprasidone is a psychotropic agent who belongs without report chemically to phenothiazine or to antipsychotic agents butyrophenone. He has a molecular weight of 412.94 (the free base), with the following chemical name: 5-[2-[4-(1,2-benzisothiazol-3-yl) - 1-piperazinyl] the ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one.
The Capsules of GEODON contain a monohydrochloride, a salt of monohydroxide of ziprasidone. Chemically, ziprasidone the monohydroxide of hydrochloride is 5-[2-[4-(1,2-benzisothiazol-3-yl) - 1-piperazinyl] the ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one, monohydrochloride, the monohydroxide. Empirical formula is C21H21CLN4OS · HCL · H2O and its molecular weight is 467.42. The monohydroxide of hydrochloride of Ziprasidone is a white in the slightly pink powder.
The Capsules of GEODON are given for the oral administration in the (white / white) (blue / white) capsules and of 80 mgs (blue / blue), of 60 mgs (blue / white), of 40 mgs of 20 mgs. The Capsules of GEODON contain the monohydroxide of hydrochloride ziprasidone, the lactose, the pregelatinized the starch and the magnesium stearate.
GEODON for Injection contains a form of lyophilized of ziprasidone mesylate trihydrate. Chemically, ziprasidone mesylate trihydrate the ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one is 5-[2-[4-(1,2-benzisothiazol-3-yl) - 1-piperazinyl], methanesulfonate, trihydrate. Empirical formula is C21H21CLN4OS · CH3SO3H · 3H2O and its molecular weight is 563.09.
GEODON for Injection is available in a vial of simple dose as ziprasidone mesylate (20 mgs ziprasidone / mL when reconstructed according to the instructions of tag - see Preparation for the Administration) for the intramuscular administration. Every millilitre of ziprasidone mesylate for injection (when reconstructed) contains 20 mgs of ziprasidone and 4.7 mgs of acid methanesulfonic solubilized of 294 mgs of sulfobutylether β-cyclodextrin the sodium (SBECD).
The Capsules of GEODON contain a monohydrochloride, a salt of monohydroxide of ziprasidone. Chemically, ziprasidone the monohydroxide of hydrochloride is 5-[2-[4-(1,2-benzisothiazol-3-yl) - 1-piperazinyl] the ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one, monohydrochloride, the monohydroxide. Empirical formula is C21H21CLN4OS · HCL · H2O and its molecular weight is 467.42. The monohydroxide of hydrochloride of Ziprasidone is a white in the slightly pink powder.
The Capsules of GEODON are given for the oral administration in the (white / white) (blue / white) capsules and of 80 mgs (blue / blue), of 60 mgs (blue / white), of 40 mgs of 20 mgs. The Capsules of GEODON contain the monohydroxide of hydrochloride ziprasidone, the lactose, the pregelatinized the starch and the magnesium stearate.
GEODON for Injection contains a form of lyophilized of ziprasidone mesylate trihydrate. Chemically, ziprasidone mesylate trihydrate the ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one is 5-[2-[4-(1,2-benzisothiazol-3-yl) - 1-piperazinyl], methanesulfonate, trihydrate. Empirical formula is C21H21CLN4OS · CH3SO3H · 3H2O and its molecular weight is 563.09.
GEODON for Injection is available in a vial of simple dose as ziprasidone mesylate (20 mgs ziprasidone / mL when reconstructed according to the instructions of tag - see Preparation for the Administration) for the intramuscular administration. Every millilitre of ziprasidone mesylate for injection (when reconstructed) contains 20 mgs of ziprasidone and 4.7 mgs of acid methanesulfonic solubilized of 294 mgs of sulfobutylether β-cyclodextrin the sodium (SBECD).
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
The rather old patients with the psychosis linked by insanity dealt with atypical antipsychotic medicaments are at a risk augmented by death compared with the placebo. The analyses of seventeen placebo controlled trials (the modal length of 10 weeks) in these patients revealed a risk of death in the patients treated as some medicament of 1.6 - 1.7 times when seen in the patients treated as the placebo. On the course of a controlled typical trial of 10 weeks, the rate of death in the patients treated as some medicament was 4.5 %, compared with a rate about 2.6 % in the group of placebo. Although reasons of death are varied, most dead had air to be the one or other one cardiovascular (by ex, heart failure, sudden death) or infectious (by ex, the pneumonia) in nature. Geodon (ziprasidone) is not approved for patients' treatment with the Psychosis linked by Insanity.
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