Parenteral injection

Prolonged Action Parenterals Injections. Intramuscular injections have been developed to achieve prolonged therapeutic effects. This can be accompHshed by suspension of dmg particles in oils or flowable gels, from which the dmg slowly diffuses. Aqueous suspensions can also provide such therapeutic response. In these cases, the soHd dmg crystals generally are quite water insoluble and of a controlled particle size and crystallized form. 

Water-for-Injection, which is used for parenteral injection products. 

Microspheres and microcapsules of lactide/glycolide polymers have received the most attention in recent years. Generally, three microencapsulation methods have been employed to afford controlled release formulations suitable for parenteral injection (1) solvent evaporation, (2) phase separation, and (3) fluidized bed coating. Each of these processes requires lactide/glycolide polymer soluble in an organic solvent. 

In 1880, the bacteriologist Robert Koch had noted that anthrax spores were more rapidly killed by the same concentrahons of phenol if the temperature was elevated. A former pharmacopoeial sterilizahon process heating with a bactericide used an elevated temperature, 80-100°C, maintained for 30 minutes, to ensure that quite low concentrations of bactericides would sterilize parenteral injections and eye-drops. 

The AUC is a measure of bioavailability, i.e. the amount of substance in the central compartment that is available to the organism. It takes a maximal value under intravenous administration, and is usually less after oral administration or parenteral injection (such as under the skin or in muscle). In the latter cases, losses occur in the gut and at the injection sites. The definition also shows that for a constant dose D, the area under the curve varies inversely with the rate of elimination kp and with the volume of distribution V. Figure 39.6 illustrates schematically the different cases that can be obtained by varying the volume of distribution Vp and the rate of elimination k both on linear and semilogarithmic diagrams. These diagrams show that the slope (time course) of the curves are governed by the rate of elimination and that elevation (amplitude) of the curve is determined by the volume of distribution. 

Information on the placental transfer of inhaled americium in humans is not available. Studies in animals that received parenteral injections of americium show that absorbed americium is transferred to the fetus. 

Information on the transplacental transfer of americium in humans is not available directly, but the information from experiments with americium and other actinides has been used to derive biokinetic models and perform dosimetric models for the human (NCRP 1998 NRC 1996 Sikov and Kelman 1989). Studies in animals that received parenteral injections of americium have shown that absorbed americium is transferred to the fetus (Hisamatsu and Takizawa 1983 Paquet et al. 1998 Sasser at al. 1986 Schoeters et al. 1990 Weiss et al. 1980) (see Section 3.4.2.1). Limited reports indicate that241 Am may induce fetal death and teratogenic effects in rodents (Moskalev et al. 1969 Rommerein and Sikov 1986). 

Almost 30 routes exist for administration of drugs to patients, but only a handfbl of these are commonly used in preclinical safety studies (Gad, 1994). The most common deviation from what is to be done in clinical trials is the use of parenteral (injected) routes such as IV (intravenous) and SC (subcutaneous) deliveries. Such injections are loosely characterized as bolus (all at once or over a very short period, such as five minutes) and infusion (over a protracted period of hours, days, or even months). The term continuous infusion implies a steady rate over a protracted period, requiring some form of setup such as an implanted venous catheter or infusion port. 

C. Parenteral (injected into the hody or placed under the skin) ... 

The ion-trapping mechanism provides a method of some forensic value for detecting the presence of alkaloids (e.g., narcotics, cocaine, amphetamines) in cases of death suspected to be due to overdosage of self-administered drugs. Drug concentrations in gastric contents may be very high even after parenteral injection. 

Enbrel Enbrel is used for the treatment of rheumatoid arthritis. It is supplied as a sterile, preservative-free, lyophilized powder. The powder is reconstituted with 1 mL sterile bacteriostatic water-for-injection (containing 0.9% benzyl alcohol) prior to parenteral injection. 

All botulin neurotoxins act in a similar way. They only differ in the amino-acid sequence of some protein parts (Prabakaran et al., 2001). Botulism symptoms are provoked both by oral ingestion and parenteral injection. Botulin toxin is not inactivated by enzymes present in the gastrointestinal tracts. Foodborne BoNT penetrates the intestinal barrier, presumably due to transcytosis. It is then transported to neuromuscular junctions within the bloodstream and blocks the secretion of the neurotransmitter acetylcholine. This results in muscle limpness and palsy caused by selective hydrolysis of soluble A-ethylmalemide-sensitive factor activating (SNARE) proteins which participate in fusion of synaptic vesicles with presynaptic plasma membrane. SNARE proteins include vesicle-associated membrane protein (VAMP), synaptobrevin, syntaxin, and synaptosomal associated protein of 25 kDa (SNAP-25). Their degradation is responsible for neuromuscular palsy due to blocks in acetylcholine transmission from synaptic terminals. In humans, palsy caused by BoNT/A lasts four to six months. 

While some parenteral injections, such as intravenous administration, provide rapid and predictable access to the circulation and tissues, therapeutic proteins are rapidly cleared from the system, and thus such administrations may result in very short durations of action. Regardless of route of administration, therapeutic proteins may exhibit limited distribution outside of endothelial cells lining blood vessels. This may be advantageous for thrombolytic agents, such as tissue plasminogen activator, which is used for rapid fibrinolytic actions at... 

Absorption of the quaternary carbamates from the conjunctiva, skin, and lungs is predictably poor, since their permanent charge renders them relatively insoluble in lipids. Thus, much larger doses are required for oral administration than for parenteral injection. Distribution into the central nervous system is negligible. Physostigmine, in contrast, is well absorbed from all sites and can be used topically in the eye (Table 7-4). It is distributed into the central nervous system and is more toxic than the more polar quaternary carbamates. The carbamates are relatively stable in aqueous solution but can be metabolized by nonspecific esterases in the body as well as by cholinesterase. However, the duration of their effect is determined chiefly by the stability of the inhibitor-enzyme complex (see Mechanism of Action, below), not by metabolism or excretion. 

Diphenoxylate and its metabolite, difenoxin, are not used for analgesia but for the treatment of diarrhea. They are scheduled for minimal control (difenoxin is Schedule IV, diphenoxylate Schedule V see inside front cover) because the likelihood of their abuse is remote. The poor solubility of the compounds limits their use for parenteral injection. As... 

Almost all cases of vitamin B12 deficiency are caused by malabsorption of the vitamin therefore, parenteral injections of vitamin B12 are required for therapy. For patients with potentially reversible diseases, the underlying disease should be... 

Vitamin B12 for parenteral injection is available as cyanocobalamin or hydroxocobalamin. Hydroxocobalamin is preferred because it is more highly protein-bound and therefore remains longer in the circulation. Initial therapy should consist of 100-1000 meg of vitamin B12 intramuscularly daily or every other day for 1-2 weeks to replenish body stores. 

Different allergic results have also been observed in rats and man, when linear and branched dextrans are compared. The relative activities of the two kinds of dextran can be reversed when two different, allergic phenomena are studied, such as an anaphylactoid reaction following parenteral injection, and wheal and erythema production following injection into the skin. Presumably, the relative importance of terminal and nonterminal specificities is also involved in these phenomena.146... 

Dosages and routes of administration Dextropropoxyphene is mostly administered by the oral route. Parenteral injection and rectal administration is painful and induces tissue damage. The ordinary oral doses are 65 mg of the hydrochloride and 100 mg of the napsylate. 

---