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Drug absorption is 90% complete when a time equivalent to three times the half-life has elapsed.

Both dissolution and diffusion are important parameters in defining bioavailability of species by the i.m. or s.c. routes. Soluble neutral compounds disperse from intramuscular sites according to size: Table 9.7 shows that mannitol, a small molecule, rapidly diffuses from the site of injection; insulin

Intravenous

Subcutaneous

Intradermal

Epidermis

Dermis

Subcutaneous 1 ^

Subcutaneous adipose tissue

Muscle and vein

Intravenous

Subcutaneous

Intradermal

Epidermis

Dermis

Subcutaneous 1 ^

Subcutaneous adipose tissue

Muscle and vein

Figure 9.17 Routes of parenteral medication, showing the tissues penetrated by intramuscular, intravenous, subcutaneous and intradermal injections; the needles, with bevel up, penetrate the epidermis (cuticle) consisting of stratified epithelium with an outer horny layer, the corium (dermis or true skin) consisting of tough connective tissue, elastic fibres, lymphatic and blood vessels, and nerves, the subcutaneous tissue (tela subcutanea) consisting of loose connective tissue containing blood and lymphatic vessels, nerves, and fat-forming cells, the fascia (a thin sheet of fibrous connective tissue), and the veins, arteries and muscle.

Drawing modified after David S. Quackenbush, in E. W. Martin, Techniques of Medication, Lippincott, Philadelphia, 1969.

Figure 9.17 Routes of parenteral medication, showing the tissues penetrated by intramuscular, intravenous, subcutaneous and intradermal injections; the needles, with bevel up, penetrate the epidermis (cuticle) consisting of stratified epithelium with an outer horny layer, the corium (dermis or true skin) consisting of tough connective tissue, elastic fibres, lymphatic and blood vessels, and nerves, the subcutaneous tissue (tela subcutanea) consisting of loose connective tissue containing blood and lymphatic vessels, nerves, and fat-forming cells, the fascia (a thin sheet of fibrous connective tissue), and the veins, arteries and muscle.

Drawing modified after David S. Quackenbush, in E. W. Martin, Techniques of Medication, Lippincott, Philadelphia, 1969.

disperses less rapidly; and dextran (molecular weight 70 000), as might be expected, disperses more slowly.

Molecular size is a minor factor in controlling release of drugs with molecular weights in the range 100-1000, but it assumes greater importance in proteins and other macro-molecules. Unless low molecular weight drugs

Table 9.7

Influence of molecular size on clearance

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