Subcutaneous drug administration

Parenteral drug administration means the giving of a drug by the subcutaneous (SC), intramuscular (IM), intravenous (IV), or intradermal route (Fig. 2-5). Other routes of parenteral administration that may be used by the primary care provider are intralesional (into a lesion), intra-arterial (into an artery), intracardiac (into the heart), and intra-articular (into a joint), hi some instances, intra-arterial dragp are administered by a nurse. However, administration is not by direct arterial injection but by means of a catheter that has been placed in an artery. 

Avoid the subcutaneous and intramuscular route of drug administration in patients in any form of shock... 

Parenteral administration of drugs by intravenous (IV), intramuscular (IM), or subcutaneous (SC) routes is now an established and essential part of medical practice. Advantages for parenterally administered drugs include the following rapid onset, predictable effect, predictable and nearly complete bioavailability, and avoidance of the gastrointestinal (GI) tract and, hence, the problems of variable absorption, drug inactivation, and GI distress. In addition, the parenteral route provides reliable drug administration in very ill or comatose patients. 

The major routes of parenteral administration of drugs are subcutaneous, intramuscular, and intravenous. Other more specialized routes are intrathecal, in-tracistemal, intra-arterial, intraspinal, intraepidural, and intradermal. The intradermal route is not typically used to achieve systemic drug effects. The major routes will be discussed separately. Definitions of the more specialized routes, along with additional information concerning needle sizes, volumes typically administered, formulation constraints, and types of medication administered, are summarized in Table 1. 

Ballard, B.E. (1968). Biopharmaceutical considerations in subcutaneous and intramuscular drug administration. J. Pharm. Sci 57 357-378. 

Subcutaneous and intramuscular Administration Subcutaneous and intramuscular administration can be used to deliver protein-based drugs. The absorption of drug is faster than with the oral route. The rate of absorption is... 

Intramuscular and subcutaneous injections are by far the most common means of parenteral drug administration. Because of the high tissue blood flow and the ability of the injected solution to diffuse laterally, drug absorption generally is more rapid after intramuscular than after subcutaneous injection. Drug absorption from intramuscular and subcutaneous sites depends on the quantity and composition of the connective tissue, the capillary density, and the rate of vascular perfusion of the area. These factors can be influenced by the coinjection of agents that alter local blood flow (e.g., vasoconstrictors or vasodilators) or by substances that decrease tissue resistance to lateral diffusion (e.g., hyaluronidase). 

Drug administration is a common method to study neonatal RSD. Both subcutaneous injection and oral administration are applicable. The consequence of neonatal RSD by drug depends on the dose and the way that the drug was administered, such as the treatment duration (38,49). In contrast to an adult response, RSD in the rat at age 2 weeks or younger does not produce a REM rebound to REM suppression (50). Therefore, a dose-response relationship between drug and REM suppression is not as easy to differentiate as in adult models. For uniformity, an injection of a full dose once a day may not produce the same result as an injection of this dose split into a twice-daily dose (51). One to two weeks of total treatment duration with appropriate doses has been proven to be effective in producing long-term developmental abnormalities (38). 

Etanercept is given subcutaneously in a dosage of 25 mg twice weekly. The drug is slowly absorbed, with peak concentration 72 hours after drug administration. Etanercept has a mean serum elimination half-life of 4.5 days. Fifty milligrams given once weekly gives the same area under the curve and minimum serum concentrations as 25 mg twice weekly. 

Various characteristics of the molecule influence its chances of reaching its target receptor since they influence the nature and extent of the body s effect on it. A drug s pharmacokinetic profile therefore determines the extent of the drug s opportunity to exert its pharmacodynamic effect. While there are various routes for human drug administration (oral rectal intravenous, subcutaneous, intramuscular, and intra-arterial injections topical and direct inhalation into the lungs), the most common for small-molecule drugs is oral administration, and discussions in the first part of this chapter therefore focus on oral administration. (In contrast, biopharmaceuticals are typically administered by injection, often directly into the bloodstream.)... 

On the other hand, polycyclic aromatic compounds given orally or subcutaneously are more likely to cause aplastic anemia, leukemia, and lymphatic tumors in Ah-nonresponsive mice. These effects are manifest in tissues distant from the site of drug administration. In the example of oral benzo[a]pyrene, pharmacokinetic studies have shown a 10-and 20-fold higher uptake in the marrow and spleen of Ah-nonresponsive than of Ah-responsive mice this confirms the phenomenon called "first-pass elimination kinetics."... 

As indicated in Table 2.1, drugs may be injected into veins, muscles, subcutaneous tissue, arteries, or into the subarachnoid space of the spinal canal (intrathecal). For obvious reasons, intraarterial and intrathecal injections are reserved for specialized drug administration requirements, such as regional perfusion of a tumor with a toxic drug or induction of spinal anesthesia, respectively. Therefore, the more routine injection routes are intravenous (IV), intramuscular (IM), and subcutaneous (SC). Because these three modalities involve skin puncture, they carry the risks of infection, pain, and local irritation. 

Commonly used routes of drug administration. (IV=intravenous IM=intramuscular SC= subcutaneous). 

Figure 29.2 Mean plasma concentration-time curves following either systemic (intravenous) or local (subcutaneous) administration of VB4-845 on day 1. VB4-845 was not detected at 24 hours in either mode of drug administration.

Local delivery Subcutaneously or intramuscularly applied microparticles can maintain a therapeutically effective concentration at the site of action for a desirable duration. The local delivery system obviates systemic drug administration for local therapeutic effects and can reduce the related... 

Since interferon beta-lb became available, 1443 instances of injection site reactions, 212 cases of injection site necrosis, and 10 cases of non-injection site necrosis were notified to the US Food and Drug Administration, and antibiotic therapy or surgery was required in 20-30% of patients (50). Severe necrotizing cutaneous lesions have also been attributed to subcutaneous interferon beta-la (51). 

Eight routes of drug administration were discussed in detail oral, subcutaneous, intramuscular, intravenous, inhalation, intranasal, sublingual, and transdermal. A route of administration is selected according to the drug taken and the goals and circumstances of administration. 

Intramuscular drug administration provides better and more consistent absorption than subcutaneous (s.c.) administration. The rate of absorption is highly dependent upon the blood flow to the site of administration and the solubility of the preparation administered (see Ch. 1). The blood flow to a muscle is dependent upon the cardiovascular status of the animal and the muscle chosen. The capillary density differs between different muscle groups and will increase in fit individuals (Clark et al 1992). Consequently, absorption from the... 

---