Intramuscular injection drug absorption from

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). 

The depot FGAs fluphenazine decanoate (also available in an enanthate salt) and haloperidol decanoate are esterified drugs formulated in sesame seed oil for deep intramuscular injection. Their absorption from the muscle and metabolism to the free base is sufficiently slow to cause absorption to be the rate-limiting step in determining their respective apparent half-lives. ... 

A number of important characteristics exist that distinguish drug therapy in infants from adult medication protocols. For example, after intramuscular administration, drug absorption is partially dependent on blood flow in the muscle bed. Abnormal drug absorption following intramuscular injection can occur in premature infants, in whom muscle mass is small and blood flow to the musculature is poor. Examples of adverse effects attributed to altered drug absorption are the reactions of infants to cardiac glycosides and anticonvulsants. 

Drug absorption from an intramuscular injection site is mainly determined by the formulation of the parenteral preparation and is influenced by the... 

Figure 2.5 Stages in drug absorption from an extravascular administration site (stomach, small intestine, intramuscular injection). Only drug in solution is absorbed. If the rate of dissolution (K2) is less than the rate of absorption (K3) then the rate at which drug is released from the dosage form controls absorption. This permits modified or sustained-release formulations, but can also lead to bioequivalence problems.

Aminoglycosides are absorbed rapidly after intramuscular injection. In critically ill patients, especially those in shock, drug absorption from intramuscular sites may be reduced by poor perfusion. 

The absorption and excretion of carbenicillin in man has been reported [396]. The antibiotic is not absorbed intact from the gut intramuscular injection (which is painful) often provides adequate serum levels (approximately 20 Mg/ntl) but infections with Pseudomonas strains having minimum inhibitory concentrations up to, or higher than, 100 Mg/ml require intravenous thbrapy to achieve such levels. No evidence of active metabolite formation has been obtained. Marked reductions in the half-life (and serum levels) of carbenicillin follow extracorporeal dialysis or peritoneal dialysis, the former producing the most striking effect [397]. These results were, of course, obtained in patients with severe renal failure. Patients with normal renal function rapidly eliminate the drug but, as with all penicillins, renal tubular secretion can be retarded by concurrent administration of probenecid. 

Absorption of phenytoin is highly dependent on the formulation of the dosage form. Particle size and pharmaceutical additives affect both the rate and the extent of absorption. Absorption of phenytoin sodium from the gastrointestinal tract is nearly complete in most patients, although the time to peak may range from 3 to 12 hours. Absorption after intramuscular injection is unpredictable, and some drug precipitation in the muscle occurs this route of administration is not recommended for phenytoin. In contrast, fosphenytoin, a more soluble phosphate prodrug of phenytoin, is well absorbed after intramuscular administration. 

The advantages of administration by intramuscular injection are that the muscle can act as a depot, and the rate of disappearance of drug from the site of injection can be calculated. Inhalational, intranasal, and intratracheal administration are normally reserved for vapors and aerosols including anesthetics. Absorption is facilitated by small-sized particles, high lipid solubility, sufficient pulmonary blood flow, and a large absorptive surface area, as it is present in healthy lungs. Administration by these routes can be very rapid when several of the factors favoring increased absorption are combined. 

Intramuscular and subcutaneous administration involves absorption from the injection site into the circulation by passive diffusion. The rate of absorption is limited by the size of the capillary bed at the injection site and by the solubility of the drug in the interstitial fluid.3 If blood flow is increased at the administration site, absorption will be increased. Conversely, if blood pressure is decreased for any reason (such as cardiogenic shock) absorption will be prolonged. 

Neurotoxicity from artemether is related to drug accumulation due to slow and prolonged absorption from intramuscular injection sites. In mice, high doses of intramuscular artemether (50-100 mg/kg/day for 28 days) resulted in an unusual pattern of selective damage to certain brain-stem nuclei, especially those implicated in hearing and balance (30). 

Cocaine HCl is an alkaloid derived from the leaves of the South American coca plant. The free base alkaloid, made by extraction from cocaine HCl, is relatively insoluble in water, but dissolves in a variety of organic solvents. There has been a dramatic increase in the use of cocaine free base, which is most commonly known by its street name "crack". Since free base is not destroyed by heating, but rather vaporizes, it can be smoked and inhaled [129]. This provides speedy absorption from the respiratory tract inducing a short-lived but rapid euphoria. The free base is also well absorbed by nasal, vaginal, gastrointestinal and subhngual mucous membranes. Cocaine can be injected intravenously, intramuscularly or subcutaneously. Crack is often combined with heroin or other drugs of abuse and taken intravenously [128]. Cocaine is detoxified by cholinesterases and cocaine or its metabolites may be present in the urine for one to two days after use. 

Drugs in aqueous solution are absorbed rapidly following intramuscular (i.m.) injection, although this varies depending on factors such as the blood flow to the injection site. In humans, absorption from the deltoid or vastus lateralis muscles is faster than from the gluteus maximus. Absorption from this site is slower in females than in males. This has been attributed to sex differences in the distribution of subcutaneous fat, since fat is a relatively poorly perfused tissue. 

Chloramphenicol is well absorbed from the gastrointestinal tract peak serum concentrations are reached 1 or 2 h after an oral dose. Peak serum concentrations after ingestion equal those achieved after intravenous administration. Absorption after intramuscular injection is highly variable with peak concentrations achieved being 5-65% of those reached after intravenous or oral administration. The apparent volume of distribution is 0.6-1.61 kg Approximately 50% of the drug is bound to plasma proteins (primarily albumin). Chloramphenicol diffuses into breast milk and readily crosses the placenta fetal blood levels are 30-80% of maternal serum concentrations. Inactivation occurs primarily by hepatic glucuronidation. Hepatic insufficiency is known to decrease metabolism but rarely requires dose modification. Chloramphenicol has an elimination half-life of 1-4 h. Urinary excretion of unchanged... 

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