Oral systems

PVDE is a nontoxic resin and may be safely used in articles intended for repeated contact with food (190). Based on studies under controked conditions, including acute oral, systemic, subchronic, and subacute contact implantation and tissue culture tests, no adverse toxicological or biological response has been found in test animals (191,192). PVDE is acceptable for use in processing and storage areas in contact with meat or poultry products prepared under federal inspection and it complies with the 3-A sanitary standards for dairy equipment. 

There are two main approaches to pharmacologic intervention for pain relief oral (systemic) and topical agents. 

Oral (Systemic) Antihistamines V V V First-line therapy... 

Because of their relative ease of production and cost compared with other methods of sustained or controlled delivery, dissolution and diffusion-controlled systems have classically been of primary importance in oral delivery of medication. Dissolution systems have been some of the oldest and most successful oral systems in early attempts to market sustaining products. 

Another way of describing the L T ratio concept is that of pulmonary targeting. Drug properties that improve pulmonary targeting include slow absorption from the lungs, low oral systemic availability, and rapid systemic clearance. 

A potential drug interaction between simvastatin and danazol, causing rhabdomyolysis and acute renal insufficiency, has been reported (43). Rhabdomyolysis can occur with all statins when they are used alone and particularly when they are combined with other drugs that are themselves myotoxic or that increase the concentration of the statin. Statins are particularly susceptible to the latter effect because of their metabolism by the CYP450 system and their low oral systemic availability. 

Fluid-State PC. This PC is extracted from soybean, and its molecule contains mainly unsaturated fatty acids. Its transition temperature is approximately 0°C, and it is referred to as the fluid-state PC. The PC molecule has structure-forming properties, and is therefore used as an excipient, both in drugs and in cosmetic preparations. In addition, it is used as an pharmacologically active drug substance in oral, systemic, and topical formulations. 

In terms of oral systems for peptide delivery, modern formulation technology ensures that the activity of pepsin can be avoided by using polymeric enteric coatings to protect the target pharmaceutical peptide. These coatings are resistant to the acid environment of the stomach but dissolve when the pH rises in the small intestine. It is absolutely essential that any formulation being considered for the oral delivery of therapeutic peptides be coated with such materials to ensure that the peptide is protected from the action of pepsin. 

The main issues associated with treatment are compliance and management of side-effects. Mr GM has not tolerated previous treatments well, and this, along with the use of particular over-the-counter analgesics, may have reduced the effectiveness of his therapy. His condition has worsened and systemic therapy with or without PUVA treatment is the next step in treatment. There is substantial evidence to suggest that long-term oral/systemic therapy can be tolerated by the vast majority of patients. Mr GM has also been intolerant of completing previous therapies and monitoring of such a care plan should be attempted by his pharmacist. 

Sangalli, M.E.,Maroni, A., Zema, L., Busseli, C., Giordano, F., and Gazzaniga,A. (2001), In vitro and in vivo evaluation of oral system for time and/or site specific drug delivery, J. Controlled Release, 73,103-110. 

The pharmacokinetics and absolute oral systemic availability of zaleplon have been assessed in a partially randomized, single-dose, crossover study in 23 healthy subjects, who received intravenous infusions of zaleplon 1 and 2.5 mg during the first and second periods and were then randomly assigned to receive an oral dose of 5 mg or an intravenous infusion of 5 mg in a crossover design (7). The oral and intravenous doses of zaleplon were well tolerated. Somnolence, abnormal vision, diplopia, and dizziness were the most commonly reported adverse events. 

Methadone is an MOR(OP3, i) receptor agonist with pharmacological properties similar to those of morphine. It is an attractive alternative MOR opioid receptor analgesic, because of its lack of neuroactive metabolites, a clearance that is independent of renal function, good oral systemic availability, a longer half-life with fewer doses needed per day, and extremely low cost. It is mainly metabolized by CYP3A4. 

Abacavir has good oral systemic availability and penetrates the nervous system. It does not interfere with drugs that are metabolized by liver microsomal cytochrome P450 (1). It has no other significant drug interactions and can be administered without food restrictions. 

Pre-treatment for 4 weeks with cimetidine 1 g/day increased the oral systemic availability of fluorouracil by 74% the AUC was increased by 27% and total body clearance was reduced by 28% (142). 

Since gatifloxacin has a high oral systemic availability (96%), oral and intravenous formulations are bioequivalent and interchangeable (8). It has a large volume of distribution (about 1.8 1/kg), low protein binding (about 20%), broad tissue distribution, and is primarily excreted unchanged in the urine (over 80%) (7). After daily repeated administration, there was predictable modest accumulation steady state concentrations were reached after the third dose (9). 

The HIV protease inhibitor saquinavir has hmited and variable oral systemic availability and ritonavir, an inhibitor of CYP450 and P glycoprotein, is widely used to increase its systemic exposure. A small pilot study in three HIV-infected patients has suggested that oral itraconazole can have similar effects on the oral availability of saquinavir (109). Concomitant use of itraconazole 200 mg/day with a combination of saquinavir and two nucleoside reverse transcriptase inhibitors led to a 2.5-to 6.9-fold increase in the AUC of saquinavir, a 2.0- to 5.4-fold increase in peak plasma concentrations, and a 1.6-to 17-fold increase in trough plasma concentrations. The effect of itraconazole on saquinavir was comparable to that of ritonavir. 

Zanamivir has poor oral systemic availability. Intranasal administration slightly increases its availability, but in mice strongly reduced viral replication (4). In vitro, zanamivir does not significantly inhibit human lysosomal neuraminidases, and so the potential for severe adverse effects is low (5). 

The interaction of tacrolimus with rifampicin has been convincingly confirmed in six healthy volunteers who took a single oral or intravenous dose of tacrolimus (112). Rifampicin 600 mg/day for 18 days produced a significant 47% increase in tacrolimus clearance after intravenous administration and a 51% reduction in its oral systemic availability, consistent with induction by rifampicin of both hepatic and intestinal metabolism of tacrolimus. 

The pharmacokinetics and absolute oral systemic availability of zaleplon have been assessed in a partially randomized, single-dose, crossover study in 23 healthy subjects, who received intravenous infusions of zaleplon 1 and 2.5 mg during the first and second periods and were... 

Bouhifd M, Bories G, Casado J, Coecke S, Norlen H, Parissis N, Rodrigues RM, Whelan MP (2012) Automation of an in vitro cytotoxicity assay used to estimate starting doses in acute oral systemic toxicity tests. Food Chem Toxicol 50 2084-2096... 

Depending on the location of ocular inflammation, a specific corticosteroid in a specific dosage form may be chosen. For instance, a corticosteroid of high potency, such as prednisolone acetate, fiuorometholone, or dexamethasone, may be chosen for deep-seated inflammation of the uveal tract. Further treatment of such inflammation may take the form of subtenon injections or oral (systemic) administration of selected corticosteroids, depending on the indication and the dosage forms available. For inflammation of a more superficial nature, the lower strengths of prednisolone acetate or the lower-potency corticosterioids, such as hydrocortisone or medrysone, will usually be chosen. 

Occasionally anecdotal data come to light on the cash outlays required for the development of specific NCEs. For example, in depositions filed for a patent infringement lawsuit, Genentech claimed it had spent 45 million to develop Protropin , its human growth hormone product, (494) and Eli Lilly certified that it had spent 16 million between 1980 and 1987 on its effort to develop its version of the drug (495). In another example, a 1980 report of the development cost of an oral systemic drug for chronic use estimated 21 million in outlays in the clinical period (226). Unfortunately, anecdotal estimates of this kind do not help verify industrywide costs, because they are self-selected and do not reflect the cost of failures or basic research. 

Mixed triglycerides formed by coupling of drugs to diglycerides exhibit physicochemical properties (120) and absorption characteristics (121)similar to those of natural triglycerides, resulting in a different pharmacokinetic and/or pharmacodynamic profile compared to that of the unmodified drug. Such an approach has been used to improve the oral systemic availability of phenytoin (122). 

Corticosteroids have been used to treat a variety of ocular diseases. Traditionally, delivery of corticosteroids for posterior-segment eye diseases has been achieved through oral systemic therapy and periocular injections. Oral corticosteroids have not been widely used to treat DME, but when used for posterior inflammatory uveitis, they require high concentrations to reach therapeutic levels in the posterior segment. These high doses often result in systemic side effects (24). Periocular corticosteroid administration often must be repeated and may be associated with complications such as ptosis and inadvertent needle penetration of the globe. 

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