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Sibutramine reductil - Assignment Example

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Sibutramine (Meridia®/Reductil®) Name:  Institution:  Sibutramine (Meridia®/Reductil®) Introduction Sibutramine hydrochloride monohydrate is an oral, medical agent administered for the purpose of treating obesity. The active ingredient is chemically a racemic mixture of the positive (+) and negative (-) enantiomers of cyclobutanemethanamine, 1-(4-chlorophenyl)-N, N-dimethyl-?…
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Download file to see previous pages Pharmacodynamics Sibutramine hydrochloride monohydrate acts as a neurotransmitter reuptake inhibitor, which decreased the reuptake of dopamine, norepinephrine and serotonin by 16%, 54% and 53% respectively. The inhibition of reuptake of these substances ensures that their levels increase within synaptic clefts and thereby increasing the levels of satiety. The serotenergic action, which results reuptake inhibition is particularly thought to influence appetite dynamics. The drug also has mechanism of action akin to tricyclic antidepressants, but it has not demonstrated antidepressant properties in animal studies already carried out. The pharmacological action of the drug is exerted via its secondary (M2) and primary (M1) amine metabolites. The parent compound is a powerful inhibitor of norepinephrine and serotonin in vivo, but not in vitro. On the other hand, the metabolites M2 and M1 cause the reuptake inhibition of serotonin and norepinephrine both in vivo and in vitro. The M1 and M2 metabolites also inhibit the reuptake of dopamine in vitro within the brain, but this happens at a lower potency than that of the inhibition on the other two neurotransmitters-norepinephrine and serotonin. ...
The drug undergoes first pass extensive metabolism within the liver to form di-desmethyl and mono-desmethyl metabolites (M2 and M1), which are pharmacologically active. Peak concentrations in the plasma are attained within 3 to 4 hours. Mass balance studies have shown that at least 77% of one oral dose of the drug is absorbed. Absolute bioavailability of the drug is not yet known (1, 2). Distribution: studies of radiolabeled sibutramine show extensive and rapid distribution in tissues, with the highest concentration being detected in the kidney and liver, which act as eliminating organs. In vitro M2, M1 and sibutramine are bound to human plasma proteins at rates of 94%, 94% and 97% respectively (2). Metabolism: Principal metabolism of the drug performed by cytochrome P450 (3A4) isoenzyme, which forms the desmethyl metabolites (M2 and M1). The M2 and M1 metabolites, which are active, are further converted via conjugation and hydroxylation to inactive metabolites M6 and M5. The peak radiolabeled material found in the plasma is accounted for by M6 (27%), M5 (52%), M2 (12%), M1 (6%) and unchanged sibutramine (3%). The plasma concentrations of M2 and M1 metabolites reached a state of steadiness in four days after dosing (1, 2). Excretion: an estimated 68% to 95% of the radiolabeled drug from a single dose was excreted through faeces and urine over two weeks. A majority of the excretion was through urine by approximately 77%. The main metabolites excreted through urine were M6 and M5. M2, M1 and the unchanged drug portions were not detected in urine. Hepatic metabolism is the primary excretory route for M2 and M1, whereas; M6 and M5 are excreted primarily from the kidney (2). Indications Sibutramine is indicated for weight loss and the general ...Download file to see next pagesRead More
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