Biapenem was introduced last year in Japan as a parenteral treatment for bacterial infections. This new 1-p-methylcarbapenem can be prepared by reaction of commercially available 4-nitrobenzyl protected p-methylcarbapenem enolphosphate with mercapto bicyclotriazolium chloride, obtained in 11 steps starting from hydrazine, followed by deprotection of the carboxylic acid function. Biapenem is a bacterial cell wall synthesis inhibitor with a broad spectrum in vitro antibacterial activity encompassing many Gramnegative and Gram-positive aerobic and anaerobic bacteria, including species producing P-lactamases. Like imipenem, biapenem is moderately active against Enterococcus faecalis and E. faecuim and is inactive against methicillin-resistant Staphylococcus aureus. Biapenem is stable to hydrolysis by human renal dihydropeptidase I (DHP-I) and therefore does not require the coadministration of a DHP-I Inhibitor. In clinical trials, biapenem showed good clinical and microbiological efficacy in the treatment of patients with intraabdominal, lower respiratory tract and complicated urinary tract infections. After intravenous administration, the drug is widely distributed, has linear pharmacokinetics and is mainly excreted in the urine with an elimination half-life of approximately 1 h. Biapenem is generally well tolerated, the most common adverse events being skin eruptions/rashes, nausea and diarrhea.
Dexmethylphenidate hydrochloride (psychostimulant) (32-35)
Country of Origin : USA
First Introduction : USA
Introduced by: Novartis
Trade Name : Focalin
CAS Registry No : 19262-68-
Molecular Weight: 269.77
Dexmethylphenidate, the pharmacologically effective enantiomer of d,/-methyl phenidate (Ritalin®) was developed as an improved treatment for attention deficit hyperactivity disorder (ADHD) in children. Dexmethylphenidate acts via the inhibition of reuptake of dopamine (by binding to dopamine transporter) and noradrenaline. It is thought to block dopamine and noradrenaline reuptake into the presynaptic neuron and increase neurotransmitter release into the extraneuronal space. Dexmethylphenidate, at half the usual dose of racemic methylphenidate, improved the symptoms of attention deficit hyperactivity disorder to a similar extent to methylphenidate in both home and school settings (SNAP-ADHD scores) at 3 h post dosing. Moreover, some studies showed that dexmethylphenidate has a statistically significant longer duration of action than the racemic form as measured by a behavioral scale at 6 h post dosing compared to placebo. In patients with ADHD, plasma dexmethylphenidate concentrations increased rapidly, reaching a maximum in the fasted state at approximately 1-1.5 h post-dose. The mean plasma half-life for dexmethylphenidate is approximately 2.2 h. Dexmethylphenidate is metabolized to d-a-phenyl-piperidine acetic acid, its main urinary metabolite which has negligible pharmacological activity. In vitro studies showed that dexmethylphenidate did not inhibit cytochrome P450 isozymes. Dexmethylphenidate was well tolerated; the most commonly reported adverse events (abdominal pain, headache, anorexia, insomnia) were mild in severity and consistent with those known to be associated with agents containing methylphenidate. Current labeling states that dexmethylphenidate should be administered twice daily with an interval of at least 4 hours between doses. Stimulant medications have been used for over sixty years and remain, until now, the first line pharmacological therapy for children with ADHD, demonstrating effectiveness in roughly 70% of patients.
Country of Origin : UK
First Introduction : USA
Introduced by: GiaxoSmithKiine
Outasteride (5a-reductase inhibitor) (36-41 )
Trade Name : Avodart I h i h 3
CAS Registry No : 164656-23-9 cA^^A-A
Molecular Weight : 528.54 h fi
Dutasteride was launched for the symptomatic treatment of benign prostatic hyperplasia. Dutasteride can be prepared from 3-oxo-4-androstene-17p-carboxylic acid by several ways in 6 or 8 steps. Dutasteride is a dual inhibitor of type 1 and 2 isoforms of 5a-reductase unlike finasteride, the first marketed 5a-reductase inhibitor, which only acts on type 2 isozyme. Dutasteride is a 3-fold greater inhibitor of type-2 5a-reductase than finasteride in men and has greater effect on the type-1 than on type-2 isozyme. In animal models, dutasteride exhibited superior efficacy and pharmacokinetics compared to finasteride. In patients with benign prostate hyperplasia, administration of dutasteride was shown to dose-dependently decrease serum dihydrotestosterone levels with greater efficacy as compared to finasteride (95% vs 67%). Serum testosterone levels increased with both active drugs, in conjunction with dihydrotestosterone suppression but remained within normal ranges. In long term studies, in men with moderate to severe benign prostate hyperplasia, once daily dutasteride significantly reduced prostate volume, reduced the risk of acute urinary retention and surgery by 57% and improved lower urinary tract symptoms and urinary flow measurements. After oral administration, dutasteride is rapidly absorbed, has a short distribution phase and a mean bioavailability of 60%. The high volume of distribution, combined with its low linear clearance results in a prolonged dose dependent half-life (from 3 days at low concentrations to 5 weeks at high concentrations) whereas finasteride's half-life time is approximately 10 h. Dutasteride is well tolerated and the most occurring adverse events are impotence, decrease in libido, ejaculation disorders and gynaecomastia. Unlike a-blockers which primarily act acutely on benign prostatic hyperplasia symptoms, 5a-reductase inhibitors can alter disease progression. Concomitant administration of dutasteride did not affect the pharmacokinetics of either tamsulosin or terazosin. In addition, the tolerability of both terazosin and tamsulosin were improved during combination therapy.
Ertapenem sodium (antibacterial) (42-44)
Country of Origin : Originator : First Introduction : Introduced by :
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