Subcutaneous route of administration

LAE-32, N-ethyllysergamide. Different people have observed and reported different effects, with different routes of administration. Subcutaneous administrations of from 500 to 750 micrograms have been said to produce a state of apathy and sedation. Clinical studies with dosages of 500 micrograms i.m. were felt to be less effective than the control use of 100 micrograms of LSD. And yet, oral doses of twice this amount, 1.6 milligrams, have been said to produce a short-lived LSD-like effect with none of these negatives. 

Phenothiazines, which are frequently antihista-minic as well as antipsychotic, concentrate in lung tissue after any route of administration. Subcutaneous or intravenous injection of chlorpromazine into ratSy rabbits, and guinea pigs resulted in a similar pattern of distribution (Berti and Cima 1955, Hackman et al. 1970). Studies in the cat showed similar concentrations of chlorpromazine in the lung, which remained almost constant from 1 to 48 h after intravenous injection (Gothelf and Karczmar 1963). 

Route of administration Subcutaneous or intravenous Oral tablets or liquid Oral suspension... 

Earlier studies by Wiles et al. (5) in which palytoxin was administered by various routes showed that this material was extremely toxic to rabbits, dogs, and monkeys. The effect of route of administration on toxicity varies in that intravenous (iv), intramuscular (im), and subcutaneous (sc) toxicity is high, yet intrarectal (ir) or oral (po) palytoxin is relatively ineffective. It was also observed that palytoxin... 

Subcutaneous (SC) administration of ESA produces a more predictable and sustained response than IV administration, and is therefore the preferred route of administration for both agents. Intravenous administration is often utilized in patients who have established IV access or are receiving hemodialysis. Starting doses of ESAs depend on the patient s Hgb level, the target Hgb level, the rate of Hgb increase and clinical circumstances.31 The initial increase in Hgb should be 1-2 g/dL (0.6206-1.2404 mmol/L) per month. The starting doses of epoetin alfa previously recommended are 80 to 120 units/kg per week for SC administration and 120 to 180 units/kg per week for IV administration, divided two to three times per week. The starting dose of darbepoetin alfa is 0.45 mcg/kg administered SC or IV once weekly (Table 23-3). 

Opioids maybe administered in a variety of routes including oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, and intraspinal. While the oral and transdermal routes are most common, the method of administration is based on patient needs (severity of pain) and characteristics (swallowing difficulty and preference). Oral opioids have an onset of effect of 45 minutes, so intravenous or subcutaneous administration maybe preferred if more rapid relief is desired. Intramuscular injections are not recommended because of pain at the injection site and wide fluctuations in drug absorption and peak plasma concentrations achieved. More invasive routes of administration such as PCA and intraspinal (epidural and intrathecal) are primarily used postoperatively, but may also be used in refractory chronic pain situations. PCA delivers a self-administered dose via an infusion pump with a preprogrammed dose, minimum dosing interval, and maximum hourly dose. Morphine, fentanyl, and hydromorphone are commonly administered via PCA pumps by the intravenous route, but less frequently by the subcutaneous or epidural route. 

Biologic response modifiers (BRMs) are indicated in patients who have failed an adequate trial of DMARD therapy.1 BRMs may be added to DMARD monotherapy (i.e., methotrexate) or replace ineffective DMARD therapy.22 The decision to select a particular agent generally is based on the prescriber s comfort level with monitoring the safety and efficacy of the medications, the frequency and route of administration, the patient s comfort level or manual dexterity to self-administer subcutaneous injections, the cost, and the availability of insurance coverage.23 In general, BRMs should be avoided in patients with serious infections, demyelinating disorders (e.g., multiple sclerosis or optic neuritis) or heart failure.21... 

Due to particle sizes in the micrometer range, parenteral suspensions are generally limited to either subcutaneous or intramuscular routes of administration. However, ultrafine suspensions can be approached by high-pressure homogenization [200]. The particle size obtained from this technique is in the 100 500 nm range, thus intravenous administration is possible [201]. General information on parenteral formulations is given in Chapter 12. 

Yoshimura et al. [132] studied the pharmacokinetics of primaquine in calves of 180—300 kg live weight. The drug was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously or subcutaneously and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high performance liquid chromatography. The extrapolated concentration of primaquine at zero time after the intravenous administration was 0.5 0.48 pg/mL which decreased with an elimination half-life of 0.16 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.5 0.08 pg/mL at 1.67 0.15 h after intravenous administration. The corresponding value was 0.47 0.07 pg/mL at 5.05 1.2 h after subcutaneous administration. The elimination half-lives of carboxyprimaquine after intravenous and subcutaneous administration were 15.06 0.99 h and 12.26 3.6 h, respectively. 

In rodents, copper administered by single intraperitoneal or subcutaneous injection is lethal at 3 to 7 mg Cu/kg BW (Table 3.7). Mice died when their drinking water contained 640 mg Cu/L (Table 3.7). In rats, copper accumulation in kidneys and lungs is similar regardless of route of administration (Romeu-Moreno et al. 1994). Concentrations of copper in serum of rats (Rattus sp.) reflect dietary copper concentrations in liver and kidney are directly related to serum Cu and ceruloplasmin (Petering et al. 1977). As serum Cu concentrations rise in rats, levels fall for serum cholesterol, triglycerides, and phospholipids (Petering et al. 1977). 

To examine the influence of different routes of administration of lipospheres on their immunogenicity, rabbits were immunized orally or parenterally (by subcutaneous, intraperitoneal, intramuscular, and intravenous routes) with lipospheres made of tristearin and lecithin (1 1 molar ratio) and containing the malaria antigen. The immune response obtained was followed with time for a period of 12 weeks postimmunization. 

No antibody activity was found after oral immunization in any of the individual rabbits immunized with liposphere R32NS 1-vaccine formulation. However, rabbit immunization by all parenteral routes tested resulted in enhanced immunogenicity, with increased antibody IgG levels over the entire postimmunization period. The individual rabbit immune response shows that immunization by subcutaneous injection was the most effective vaccination route among all parenteral routes of administration tested. 

Acute subcutaneous LD50 values in the rat, mouse, and cat were 463-524, 1,208, and 200-300 mg/kg, respectively, indicating that by this route of administration the cat is approximately twice as sensitive as the rat, which in turn is approximately twice as sensitive as the mouse (Clark and Litchfield 1969). 

The dosing regimens can be quite variable and at times very techniqueintensive. These chemicals are almost always administered by a parenteral route of administration normally intravenously or subcutaneously. Dosing regimens have run the range from once every two weeks for an antihormone vaccine to continuous infusion for a short-lived protein. 

Only the first three are discussed in any detail here. Most of these routes of administration place a drug directly or indirectly into systemic circulation. There are a number of these routes, however, by which the drug exerts a local effect, in which case most of the drug does not enter systemic circulation (e.g., intrathecal, intraventricular, intraocular, intraracistemal). Certain routes of administration may exert both local and systemic effects depending on the characteristics of the drug and excipients (e.g., subcutaneous). 

A third consideration is that certain routes of administration may favor immu-nogenicity of recombinant proteins. In early trials, rDNA proteins introduced by subcutaneous or intramuscular injections (procedures known to improve the immu-nogenicity of proteins) resulted in a higher frequency of antibody responses than in the intravenous route. 

Other routes of administration used less commonly in dog safety studies are subcutaneous, intramuscular, intraperitoneal, rectal, and vaginal. 

The route of administration of an NCE is typically the intended clinical route of administration. However, an alternative route may be used if this leads to an increase in systemic exposure of parent drug or major metabolites or if this alternative route satisfies another important objective of the study. For example, it is common to increase the exposure following inhalation administration by associating a subcutaneous administration of the NCE. 

The pharmacokinetics of ibogaine have not been fully elucidated (Popik and Click 1996). Its absorption, distribution, metabolism, and excretion are not fully clear. The route of administration notably affects ibogaine s efficacy, with greater effects subcutaneously than intraperitoneally (Pearl et al. 1997). The half-life of ibogaine is approximately 1 hour in rodents, and it is not detectable in the brain after 12 hours, although the assays used may have lacked sensitivity (Dhahir 1971 Zetler et al. 1972 Popik and Click 1996). 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

This effect was investigated for the route of administration (intraperitoneal or subcutaneous) and for the animal species. 

---