Absorption intramuscular

Jackson, A. J. (1981). Intramuscular absorption and regional lymphatic uptake of liposome-entrapped inulin. Drug Metab. Dispos., 9, 535-540. 

This is a medical emergency, and must be treated with intravenous hydrocortisone (50-100 mg 6-hourly) as intramuscular absorption may be unreliable. Patients are usually hypovolaemic and shocked, so mineralocorticoid deficiency must also be treated by using intravenous saline infusion, often requiring several liters of fluid, until the patient is well enough to take oral fludrocortisone. 

Oral absorption occurs in the small intestine and is dose dependent. Peak blood concentrations occur 2-4 h after single 100 mg doses but may be delayed by 4-12 h after a loading dose (600 mg). Peak levels may not occur for 2-7 days after an oral overdose. The oral bioavailability of phenytoin averages 90% (range, 70-100%). Intramuscular absorption is erratic and unpredictable. 

Percutaneous absorption may be increased substantially in newborns because of an underdeveloped epidermal barrier (stratum comeum) and increased skin hydration. The increased permeability can produce toxic effects after the topical use of hexachlorophene soaps and powders, salicyhc acid ointment, and rubbing alcohol. Interestingly, a study has shown that a therapeutic serum concentration of theophylline can be achieved to control apnea in premature infants of less than 30 weeks gestation after a topical apphcation of gel containing a standard dose of theophylline. " The use of this route of administration may minimize the unpredictability of oral and intramuscular absorption and complications of intravenous drug administration for certain drugs. 

Jernigan, Hatch, and Wilson (1988) studied the pharmacokinetics of tobramycin after intramuscular administration in cats. Bioavailability was estimated at 102.5% with maximal concentrations occurring within about an hour. Hence, tobramycin absorption appears rapid and complete. There are few papers modeling the intramuscular absorption of drugs. Swabb et al. (1983) modeled the intramuscular administration of aztreonam, another antibiotic, in humans and found that a simple first-order absorption was adequate to explain the rapid (time to maximal concentrations was 0.88 h) and complete (101% bioavailability) absorption. Similarly, Krishna et al. (2001) also found that first-order absorption was sufficient to model the pharmacokinetics of quinine after intramuscular administration. In both cases, the drugs were formulated in water. 

Chlordiazepoxide is well absorbed after oral administration, and peak blood concentration usually is reached in approximately 4 hours. Intramuscular absorption of chlordiazepoxide, however, is slower and erratic. The half-life of chlordiazepoxide Is variable but usually quite long (6-30 hours). The initial N-demethylation product, N-desmethylchloridiazepoxide, undergoes deamination to form the demoxepam (Fig. 22.18), which is extensively metabolized, and less than 1 % of a dose of chlordiazepoxide is excreted as demoxepam. Demoxepam can undergo four different metabolic fates. Removal of the N-oxide moiety yields the active metabolite, N-desmethyIdiazepam (desoxydemoxepam). This product is a metabolite of both chlordiazepoxide and diazepam and can be hydroxylated to yield oxazepam, another active metabolite that is rapidly glucuronidated... 

Intramuscular absorption is 100%, but variable depending on the site of injection (absorption 1/2 12 and 26 min from deltoid and gluteus sites, respectively). For this reason, the intravenous route of administration is preferred. ... 

When AMDs are administered parenterally as aqueous solutions (usually intramuscularly), absorption into the... 

Mustard converts to a cyclic compound within minutes of absorption into a biological milieu, and the cyclic compound reacts rapidly (ie, within minutes) with blood and tissue components.13 These reactions will take place with the components of the wound—the blood, the necrotic tissue, and the remaining viable tissue. If the amount of bleeding and tissue damage is small, mustard will rapidly enter the surrounding viable tissue, where it will quickly biotransform and attach to tissue components (and its biological behavior will be much like an intramuscular absorption of the agent). 

After oral administration, the levels of normeperidine are increased compared to systemic administration. In hepatic disease, the reduced hepatic clearance of meperidine results in increased absorption necessitating a reduction in dose. Following intramuscular administration of meperidine, the elimination half-life (f P) is 3.6 hours (3.1-4.1 hours). Intramuscular absorption is highly variable with a two-fold variation in blood levels in the same patient and a wider five fold intra-patient variability. The l P is 111.4 hours in cirrhotic patients (range 8.3-18.7), but the levels of normeperidine are reduced. The elimination half-life of meperidine and normeperidine are prolonged in patients with renal failure. The l P elimination half-life of normeperidine is anywhere from 14-21 h to 24-48 h and as long as 34 h in renal failure [3]. 

Agents capable of promoting absorption and/or permeation were discussed in a recent review . The intestinal absorption of sulfamethoxypyridazine, diphenhydramine, salicylic acid, p-hydroxybenzoic acid and heparin was facilitated in the presence of surfactants, as was the intramuscular absorption of enduracidin . The effect of sodium taurodeoxycholate on drug transport across biological barriers was studied " . Mixed micellar solutions of a fatty acid, a monoglyceride and sodium taurocholate had a greater effect on the absorption of... 

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

HYDANTOINS Fhenytoin is the most commonly prescribed anticonvulsant because of its effectiveness and relatively low toxicity. However, a genetically linked inability to metabolize phenytoin has been identified. For this reason, it is important to monitor serum concentrations of the drug on a regular basis to detect signs of toxicity Fhenytoin is administered orally and parenterally. If the drug is administered parenterally, the IV route is preferred over the intramuscular route because erratic absorption of phenytoin causes pain and muscle damage at the injection site... 

Simons PER, GuX, Simons KJ Epinephrine absorption in adults intramuscular versus subcutaneous injection. J Allergy Chn Immunol 2001 108 871- 27 873. 

It is not surprising that intramuscular injection of epinephrine into the vastus lateralis produces a prompt peak plasma epinephrine concentration, because of the large size and excellent vascularization of this muscle. It is also not surprising that subcutaneous injection of epinephrine potentially leads to delayed absorption, because of the potent Ui-adrenergic agonist vasoconstrictor effects in the skin and subcutaneous tissue, as evidenced by skin blanching at the injection site [19, 20]. 

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. 

Mineral Oil Hydraulic Fluids. Absorption of a mineral oil in an emulsion was apparently very slow in female rats injected subcutaneously with 0.1 mL and in squirrel monkeys injected intramuscularly with 0.3 mL (Bollinger 1970). The emulsion contained 1 volume mannide monoleate, 9 volumes mineral oil, and 9 volumes water [14C]labeled hexadecane, a major component of the mineral oil, was added to the emulsion as a radiotracer. At 1 week and 10 months after treatment, radioactivity remaining at the sites of injection accounted for 85-99% and 25-33%, respectively, of the administered radioactivity. 

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. 

S. Feldman, Physicochemical factors influencing drug absorption from the intramuscular site, Bull. Parenter. Drug. Assoc., 28, 53-63 (1974). 

BJ Aungst, NJ Rogers, E Shefter. (1988). Comparison of nasal, rectal, buccal, sublingual, and intramuscular insulin efficacy and the effects of a bile salt absorption promoter. J Pharmacol Exp Therap 244 23-27. 

Data on the absorption of simple salts of the lanthanide elements injected intramuscularly into rats are summarized in Figure 10.4 The dependence of the fraction remaining at the injection site on the administered mass is apparent. When the amount injected was less than 0.01 jug, about 0.5 was absorbed in the first few days another 0.4 was absorbed with a half-time of about 25 days and the remaining 0.1 left the injection site with a half-time of 100 to 200 days. As the total mass injected was increased, the fraction absorbed in the first few days declined, and the amounts associated with the lower absorption rates increased. If 100 jug or more were injected, only 0.05 to 0.1 was absorbed during the first few days, and absorption was very slow thereafter. 

Absorption of intramuscularly injected lanthanides (Durbin et al., 1956a) is greatly accelerated if they are administered as citrate complexes. However, the fractional absorption rate is still a function of the amount injected. One day after injection of < 1 jug of the lanthanide citrates, 0.95 had been absorbed 0.75 was absorbed in the first day if the amount of stable lanthanide administered was 1 to 5 jug. After 256 days, only 0.05 of the injected 152,154Eu plus 5 jug Eu remained unab-... 

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