Administration, drugs intraocular injections

Nevertheless, very limited research has been carried out to develop DDS for the posterior segment of the eye in the last decades. Whereas new antiangiogenic compounds and neurotrophic factors can open new therapeutic avenues in the treatment of AMD, retinal dystrophies and ocular manifestations of diabetes, the frequent intraocular injections of these compounds remain a problem and are associated with complications and discomfort for the patient. Thus, the need for efficient noninvasive DDS for the administration of drugs to the back of the eye is awaiting a ground-breaking multidiscipline advancement. 

Low-dose regimens frequently result in very low corticosteroid concentrations in body fluids (e.g., low pg/mL range in plasma). PK analysis that is often necessary to manage these therapies is hindered by the inadequate sensitivity by most established analytical methods. In addition, certain drug delivery strategies, such as inhalation or intraocular injection, result in systemic levels too low to be detected by current methods. Furthermore, administration of some corticosteroid prodrugs, such as these in the forms of acetates/propionate, often results in sustained, low concentrations in plasma. Therefore, a highly sensitive and selective analytical approach is necessary for cases in which sustained low concentration of corticosteroids may be present systemically or in tissues. 

Topical instillation 218 Periocular injections 220 Intraocular injections 220 Parenteral administration 220 Innovative drug delivery systems 221... 

There are several other examples of truly unique formulations or routes of administration that we may expect to be further exploited in the future. AIDS-associated infective retinitis is treated with a drug administered by intraocular injection, and the current parlous state of retinal detachment treatments suggests that this route of administration may find wider use. It turns out that cell membranes become leaky when exposed to high voltages otherwise insoluble or excluded drugs can enter the cell under these conditions, and this uses a multi-tined stimulator, known as an electropora-tor. Needleless injectors have been available for decades, yet still seem to be under-used (the needleless injector used by Dr Bones McCoy of the USS Enterprise" is clockwork, develops several thousand pounds pressure per square inch, and feels like a mild middle-finger percussion when used over the deltoid). 

Therefore, ocular iontophoresis seemed to be the answer to the low bioavailability of drugs after topical administration and to the potential serious complications after intraocular injections used for the treatment of many eye disorders. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

Sustained delivery of ophthalmic medications is a novel approach in treating chronic intraocular infections in conditions where systemic administration is accompanied by undesirable side-effects and repeated intravitreal injections carry the risk of infection. The administration of medications by implants or depot devices is a very rapidly developing technology in ocular therapeutics. The various types of implant and mechanisms of drug release have been discussed in general in Chapter 4. 

Hydrophilic drugs, such as gentamicin, do not cross the blood-retinal barrier readily after systemic administration. After intravitreal administration they have a prolonged half-life of 24 hours or more in the vitreous humor.Their major route of exit is across the lens zonules and into the aqueous humor and then through the aqueous outflow pathways. For the vitreous to act as a depot for these drugs, the agents must be injected, introduced by iontophoresis, or slowly released by a surgically implanted intraocular device. 

The formulation chosen for particular drugs is not random, but the degree to which it is critical varies from drug to drug. For example, hydrocortisone is available for at least seven routes of administration, as tablets, several creams and ointments, intraocular solutions, suppositories, intrarectal foams, injections and eardrops. Even newer drugs, with fewer indications than hydrocortisone, seek greater market acceptability by providing a variety of alternative formulations (e.g. sumatriptan is available as an injection, intranasal spray, suppository and tablets). 

The series of clinical trials that led to approval by the U.S. Food and Drug Administration involved 430 eyes in 330 patients. Fomivirsen significantly delayed progression of CMV retinitis in patients with AIDS, including those who had failed treatment with ganciclovir or foscarnet, the first-line therapies. Fomivirsen is administered by intravitreal injection at doses of 165 pg once weekly for three weeks of induction and then once every two weeks. It also can be administered In a dose of 330 pg on days 1 and 15 and then once a month thereafter. Mean maximum retinal concentrations of fomivirsen occur at 2 days, and the elimination half-life after a single, 115-pg dose in monkey retina was 78 hours. There are no systemic side effects. Ocular side effects include Increased intraocular pressure and mild to moderate intraocular inflammation that can be reversed with topical steroid treatment. It is important that side effects be minor, because treatment will be lifelong. 

Most ocular diseases like dryness, conjunctiva, and eye flu are treated by topical drug application in the form of solutions, suspensions, and ointment. In the earlier period, drug delivery to the eye has been limited to topical application, redistribution into the eye following systemic administration, or direct intraocular/periocular injections. However, one of the major barriers of ocular medication is to obtain and maintain a therapeutic level at the site of action for a prolonged period of time. 

B V ara U is a newly-developed antiviral drug particularly effective to varicella zoster virus. No changes in the b-wave, the c-wave or the oscillatory potentials were induced by an intravitreal injection of 100 pig BV area U or by intravitreal irrigation with 20 pig/m BV ara U. The concentration of BV ara U after an oral administration was much lower in the vitreous than in the serum, which indicates that intraocular penetration of B V ara U is very poor. Furthermore, an enteral use of B V ara U in conjunction with some of antimetabolites reportedly causes serious systemic adverse effects. Therefore, a topical intraocular application of BV ara U is much preferable. 

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