Dosage Forms and Routes of Administration

Because of clinical need, the species involved, or the needs of herd- or flock-scale treatment, drug preparations for food-producing animals are presented in dosage forms that vary greatly. A plethora of different main dosage forms are 

Other less frequently used parenteral routes such as intra-articular or sub-conjuctival injections and intramammary or intrauterine infusions have limited application they aim at directly placing high drug concentrations close to the site of infection. These routes of administration differ from the major parenteral routes in that absorption into the systemic circulation is not a prerequisite for delivery of drug to the site of action. When the infection site is relatively inaccessible, such as in the case of mastitis, the combined use of systemic and local delivery of drug to the site of infection may represent the optimum approach to treatment. 

Most oral preparations are solid dosage forms that need to be dissolved before they can be absorbed. The inert ingredients of such dosage forms can have a profound effect on the dissolution of the active ingredient and thereby control its rate of absorption. In addition, the drug may be unstable in the gastrointestinal fluids, as in the case of penicillin G, or metabolized. 

Metabolism may be mediated by intestinal microflora, epithelial enzymes, or liver enzymes preceding entry into the systemic circulation. Chloramphenicol is well absorbed when administered orally to calves less than 1 week old, but it is inactivated by microflora when administered to ruminants. Similar observations have been made after oral administration of amoxicillin, ampicillin, and cephalexin therapy in young calves (11). On the other hand, trimethoprim, which is extensively metabolized in the liver and may undergo some metabolism in the rumen, shows higher systemic availability in the newborn calf and kid, due probably to the lower metabolic activity in the neonatal animal. 

Medina, in Veterinary Drug Residues, Food Safety (W.A. Moats, and M.B. Medina, Eds.), American Chemical Society, Washington, D.C., p. vii (1996). 

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The physical characteristics should be considered (in combination as appropriate) in relation to the proposed dosage form and route of administration. Factors to be considered extend to solubility characteristics, crystal form and properties, moisture or solvent content, particle size and size distribution (which may affect bioavailability, content uniformity, suspension properties, stability, and preclinical or clinical acceptability), polymorphism, etc. 

Patients currently receiving theophylline products - Determine, where possible, the time, amount, dosage form, and route of administration of the last dose the patient received. 

CDER-approved products are considered those subject to an approved NDA or ANDA. Some information on which components/materials aie used in CDER-approved products is available from the Agency (e.g., FDA, CDER, Inactive Ingredient Guide, 1996, Division of Drug Information Resources). When infonnation is not available, an applicant should use reliable sources of infonnation to determine that the component or material has been used in and has been in contact with a CDER-approved product of the same dosage form and route of administration, as appropriate. The applicant should identify in the supplement or annual report the basis for the conclusion that the component or material is used in a CDER-approved product. 

Pharmacokinetic principles, in addition to clinical factors such as the state of the patient, are utilized in determining dosage regimens. Factors that relate to the safety and efficacy of the drug, such as activity-toxicity relationships (therapeutic window and side effects), and pharmaceutical factors, such as dosage form and route of administration, must be considered.16... 

Method development includes feasibility and optimization to meet the predefined study requirements. The appropriate standard calibrator range and concentrations of VS and QC (see discussion below) should be established for the dosage form and route of administration. The lessons learned during method development are critical for the development of specific parameters for the performance of the assay. For example, the number of validation batches and acceptance criteria should be described in a validation plan, and the standard operating procedure (SOP) should be written before conducting the pre-study validation. The correct approach should be to develop a valid (acceptable) method, rather than simply... 

Drug products can be considered to be pharmaceutical equivalents if such products (1) contain the same active ingredients, (2) are of the same dosage form and route of administration, and (3) are identical in strength and concentration. The term therapeutic equivalence is also used to describe pharmaceutical equivalence. Pharmaceutically equivalent drag products may differ in attributes such as shape, color, excipients, and release mechanisms. Pharmaceutical equivalence is of importance in the development of generic drags. See http //www.fda.gov. 

Table 19 Dosage forms and routes of administration of avermectins to various animal species...

Generic Substitution The substitution of drug products that contain the same active ingredients and are chemically identical in strength, concentration, dosage form, and route of administration to the drug product prescribed. 

It is this parameter that ultimately determines the activity, toxicity, stability and dosage form, and route of administration. The United States Pharmacopoeia (USP) classifies drugs based on their solubility (Table 4). 

Match np the strength and dosage form and route of administration so that the same products are being compared (pharmaceutical equivalent). 

The absorption rate constant is a constant for a given drug formulation, dosage form and route of administration. That is, the same drug... 

Note Peak plasma concentration is always directly proportional to the dose administered, regardless of the route of administration or the health of the subject (healthy or renally impaired) as long as a first-order process is occurring. Therefore, administration of a 500 mg dose of the same drug via identical formulation, dosage form and route of administration will give a y-intercept of 7 mg % and a peak plasma concentration of 2.898 mg % (2.898 mg 100 mL ). The peak plasma concentration in a renally impaired subject will be higher than in a normal subject nonetheless, it will be directly proportional to the administered dose. 

No malformations were found in fetuses of rats treated with doses up to 10.3 g/kg prepared Sichuan aconite, although the body weight and food consumption were reduced in the pregnant rats. Fetuses of rats administered 8.3 g/kg of Aconitum kusnezoffii had a reduction in body length and breastbone calcification (Xiao et al. 2005). The dosage form and route of administration used in this study was not specified in the English language abstract but is likely to have been a decoction administered orally (Xiao et al. 2005). 

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