In 2001, drugs for cancer dominated new introductions. The 32 new drug
approvals not only focused on enhancing the prevalent treatment options but also incorporated new research technologies in drug delivery systems. This article reviews the new molecular entities.

ANTI CANCER
Imatinib mesylate, approved for treatment of chronic myeloid
leukaemia (CML) is the first convincing example of a 'rationally designed' drug that turned out to be impressively effective in treating leukaemia. Imatinib inhibits the BCR-ABL tyrosine kinase created by CML, responsible for causing uncontrollable proliferation and reduced apoptosis of white blood cells.
The approval of imatinib mesylate opens the door to an era of molecularly targeted therapy for all malignancies, hopefully solving the 'pan toxicity' problem of widely used chemotherapy agents.

Zoledronic acid received approval for the treatment of hypercalcemia of malignancy, a common life-threatening metabolic complication. Zoledronic acid acts by inhibiting increased osteoclastic activity and also induces osteoclast apoptosis, thereby reducing the associated loss of calcium.

Alemtuzumab, a lymphocyte that depletes humanised monoclonal antibody is indicated in the treatment of chronic lymphocytic leukaemia (CLL). Alemtuzumab is found to be effective against CLL refractory to chemotherapy, with an acceptable toxicity profile.

PULMONARY/RESPIRATORY DISEASES
Tiotropium bromide is a novel compound that works through prolonged M3-receptor antagonism. It is indicated for the maintenance treatment of patients with COPD. COPD is an all-inclusive term that refers to a set of symptoms including chronic cough, expectoration, exertional dyspnoea and a significant, progressive reduction in airflow that may or may not be partly reversible. Smoking is the leading cause of COPD, but exposure to pollution and genetic predisposition are known risk factors. Clinical trials indicate tiotropium to be superior to ipratropium bromide.

ALLERGY
Levocetrizine, a new highly effective and well-tolerated anti-histamine was introduced for treatment of symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and chronic idiopathic urticaria. Levocetrizine, being the potent single isomer of cetrizine, binds twice as strongly to histamine H1 receptors in vitro and has a highly consistent and predictable anti-histamine action.
Desloratidine, an active metabolite of loratidine is indicated for the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria (CIU) in adults and children above 12 years old. Desloratidine possesses pharmacodynamic activity similar to that of loratidine but has a relative potency 10 to 20 times greater than loratidine.

ANTI INFECTIVES
Caspofungin acetate is the first introduction in a new class of antifungals, called echinocandins, in more than a decade. Caspofungin acetate, a glucan synthesis inhibitor, is approved for the intravenous treatment of invasive aspergillosis in patients not responsive to antifungal therapies. Ertapenem sodium, a once daily injectable antibiotic for adults was approved for the treatment of moderate to severe infection by gram positive and gram negative aerobic and anaerobic bacteria causing, skin, urinary tract, kidney intra-abdominal and post-surgical gynaecological infections.

UROLOGY
Dutasteride, a 5-a reductase inhibitor was approved for the treatment of symptomatic benign prostate hyperplasia (BPH). Dutasteride blocks both type1 and type2 5-a reductase isoenzymes, which convert testosterone to dihydrotestosterone, the androgen responsible for development of BPH.

NEUROLOGY
Amlotriptan malate was introduced in the year 2001 for acute treatment of migraine with or without aura in adults. Amlotriptan malate is an addition to the prevalent class of triptans, which are selective serotonin receptor agonists.
Frovatriptan malate, another 5-HT 1B/1D receptor agonist was approved for acute treatment of migraine. Frovatriptan malate offers a unique benefit in terms of improved half-life (26 hours) as compared to other triptans, which have a half-life of six hours or less.

AIDS
The first nucleotide analogue for HIV treatment, tenofovir disoproxil fumarate was granted approval for the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents.
Tenofovir disoproxil fumarate is the first nucleotide analogue reverse transcriptase inhibitor approved for the treatment of HIV.

OPTHALMOLOGY
Two new treatment options, travoprost and bimatoprost were introduced last year to treat elevated intraocular pressure, which is often associated with glaucoma. Glaucoma, a leading cause of irreversible blindness in the world is associated with optic nerve damage and visual field changes. Elevated IOP is a primary risk factor for glaucoma and its management can usually prevent vision loss. Travoprost and bimatoprost ophthalmic solutions are synthetic prostaglandin analogs, which lower the intraocular pressure by increasing the drainage of aqueous humour from the eye.
Valganciclovir gained an approval for the treatment of AIDS related cytomegalovirus retinitis, an infection of the eye that leads to blindness. Valganciclovir, a prodrug of ganciclovir, which exists as a mixture of two diastereomers, inhibits the replication of human cytomegalovirus in vitro and in vivo.

DERMATOLOGY
Dermagraft, a human based, mass-produced, cryopreserved living dermal substitute, received approval for treatment of chronic foot ulcers in patients with diabetes. Dermagraft, a product of tissue engineering is constructed from human cells known as fibroblast placed on a dissolvable mesh material. When dermagraft is placed on the ulcer, the mesh material is gradually absorbed and human cells grow into place, replacing the damaged skin.
Pimecrolimus is the first non-steroid licensed for the treatment of atopic dermatitis and one of the first new treatments since topical corticosteroids were introduced 50 years ago. The drug acts by inhibiting T-cell activation and by preventing the release of inflammatory cytokines.

RHEUMATOLOGY/NSAIDS
Valdecoxib a new cox-2 inhibitor was approved for once a day treatment regimen for osteoarthritis (OA), adult rheumatoid arthritis. Valdecoxib is an NSAID that exhibits anti-inflammatory, analgesic and antipyretic properties. It inhibits cyclooxygenase-2, thereby inhibiting prostaglandin synthesis. and is well tolerated.
Risedronate sodium is indicated for the prevention and treatment of postmenopausal and corticosteroid induced osteoporosis. Risedronate prevents postmenopausal bone loss, decreases fracture associated with post menopausal osteoporosis and effectively treats Paget's disease.

HAEMATOPOETIC SYSTEM
A longer acting version of the leading treatment for anaemia, darbepoetin alfa was introduced for anaemia associated with chronic renal failure. Darbepoetin alfa requires less frequent dosing as compared to the existing therapy epoetin alfa.
Bivalirudin, a thrombin-specific anticoagulant was approved to treat patients with unstable angina pectoris, undergoing percutaneous transluminal coronary angioplasty in conjunction with aspirin therapy.

CARDIOVASCULAR SYSTEM
Nesiritide is a recombinant form of human B type natriuretic peptide (hBNP), a naturally occurring hormone secreted by ventricles. It was approved for the intra-venous treatment of subjects with acutely decompensated congestive heart failure, suffering shortness of breath at rest or with minimal activity.
Bosentan, an oral active endothelin receptor antagonist is indicated in treatment of subjects suffering from pulmonary arterial hypertension (PAH) characterised by elevated levels of endothelin in lungs and plasma.

GYNAECOLOGY
Norelgestromin / ethinyl estradiol is the first transdermal hormonal patch as well as a non-invasive form of birth control. It was introduced as a once-a-week contraceptive for women. It acts through suppression of the gonadotrophin hormone.

IMPORTANT DRUGS INTRODUCED IN INDIA IN 2001