Intramuscular injections of drugs

Schou, J. (1971). Subcutaneous and intramuscular injection of drugs. In Handbook of Experimental Pharmacology (Brodie, B.B. and Gillette, J.R., Eds.). Springer, Berlin, Ch. 4. 

Rasmussen, F. Tissue damage at the injection site after intramuscular injection of drugs in food-producing animals. In Trends in Veterinary Pharmacology and Toxicology van Miert, A.S.J.P.A.M., Frens, J., van der Kreek, F.W., Eds. Elsevier Amsterdam, 1980 27-33. 

Toutain, P.-L. Lassourd, V. Costes, G. Alvinerie, M. Bret, L. Lefebvre, H.P. Braun, J.P. A non-invasive and quantitative method for the study of tissue injury caused by intramuscular injection of drugs in horses. J. Vet. Pharmacol Ther. 1995, 18, 226-235. 

Ohaegbulam SC. Peripheral nerve injmies from intramuscular injection of drugs. West Afr J Pharmacol Drug Res 1976 3(2) 161-7. 

Colchicine (a drug used in treatment of gout) and vinblastine (a cancer chemotherapy agent) may decrease liver uptake of americium. In rats that received an intraperitoneal injection of either colchicine and vinblastine prior to an intravenous or intramuscular injection of americium citrate, liver uptake of americium was lower, relative to controls, and kidney and skeletal americium uptake were higher (Seidel 1984, 1985). The effect is thought to involve disruption of hepatic microtubule formation, which is critical to the formation and intracellular processing of lysosomes, the initial site of accumulation of americium in the liver. 

Intramuscular haloperidol is a suitable drug for tranquillizing violent patients, but it can be difficult to determine the correct dosage, and there is the risk of an acute dystonic reaction, particularly in younger patients. The British National Formulary recommends intramuscular injections of from 2 to 10 mg, subsequent doses being given after 4-8 hours but in exceptional cases, initial doses of up to 30 mg may be necessary. 

Heparin is prescribed on a unit (lU) rather than milligram basis. Tlie dose must be determined on an individual basis. Heparin is not absorbed after oral administration and therefore must be given parenterally. Intravenous administration results in an almost immediate anticoagulant effect. There is an approximate 2-hour delay in onset of drug action after subcutaneous administration. Intramuscular injection of heparin is to be avoided because of unpredictable absorption rates, local bleeding, and irritation. Heparin is not bound to plasma proteins or secreted into breast mUk, and it does not cross the placenta. 

Polymyxin B and colistin are not well absorbed from the gastrointestinal tract. An intramuscular injection of the polymyxins results in high drug concentrations in the liver and kidneys, but the antibiotic does not enter the cerebrospinal fluid (CSF), even in the presence of inflammation. 

Topiramate, another antiepileptic drug, may also be helpful in a dose of 400 mg daily, built up gradually. Small quantities of alcohol may suppress essential tremor but only for a short time. Alprazolam (in doses up to 3 mg daily) or gabapentin (100-2400 mg/d) is helpful in some patients. Others are helped by intramuscular injections of botulinum toxin. Thalamic stimulation by an implanted electrode and stimulator is often worthwhile in advanced cases refractory to pharmacotherapy. Diazepam, chlordiazepoxide, mephenesin, and antiparkinsonism agents have been advocated in the past but are generally worthless. Anecdotal reports of benefit from mirtazapine were not confirmed in a double-blind study, which found no effect on the tremor in most patients. 

Benzathine penicillin and procaine penicillin G for intramuscular injection yield low but prolonged drug levels. A single intramuscular injection of benzathine penicillin, 1.2 million units, is effective treatment for 3-hemolytic streptococcal pharyngitis given intramuscularly once every 3-4 weeks, it prevents reinfection. Benzathine penicillin G, 2.4 million units intramuscularly once a week for 1-3 weeks, is effective in the treatment of syphilis. Procaine penicillin G, formerly a work horse for treating uncomplicated pneumococcal pneumonia or gonorrhea, is rarely used now because many strains are penicillin-resistant. 

Following intramuscular injection of chloramphenicol in sheep, the withdrawal period down to the level of 0.05 ppm was estimated at 14.4 days for the injection site, 6 days for noninjected muscle, 9 days for fat, 11 days for kidney, and 11 days for the liver (32). When chloramphenicol was administered to rabbits, muscle and kidney were the tissues containing the highest levels of the parent drug at 6 h postdosing, whereas at 24 h only muscle contained detectable amounts of residues (33). 

The metabolism of danofloxacin does not differ in swine. When five daily intramuscular injections of 1.25 mg radiolabeled danofloxacin/kg bw were given to pigs, the parent drug accounted for 72-81 % of the radioactivity excreted in feces and urine over the 5- day dosing period (143). In feces, 5-7% of the radioactivity was identified as A-desmethyl danofloxacin. In urine, 2-3% was A-desmethyl danofloxacin, 10-14% danofloxacin-A-oxide, and 3% danofloxacin glucuronide. 

Residue depletion studies in pigs given three daily intramuscular injections of 1.25 mg danofloxacin/kg bw showed that residues of the parent drug in liver were 27 ppb at 2 days after the last dose and below 10 ppb at later time points. Mean danofloxacin concentrations in kidney declined from 36 ppb at 2 days after the last dose to 5.5 ppb at 6 days after the last dose and to below 5 ppb at later time points. Two days after the last dose, mean danofloxacin concentrations in muscle, fat, and at the injection site were 15 ppb, below 5 ppb, and 17 ppb, respectively at later time points residues could not be detected. Residues of A-... 

Following a single intramuscular injection of oxytetracycline to European eels at a dosage of 60 mg/kg bw, maximum plasma oxytetracycline concentration (113 ppm) were achieved between 8 and 16 h after administration (240). At 3 weeks after drug administration, highest residue concentrations were in liver (21.7 ppb) and bones (30.2 ppb), whereas kidney, spleen, and muscle contained 6.0, 5.5, and 3.6 ppb. This experiment demonstrated that the pharmacokinetic profile of intramuscularly injected oxytetracycline to eel differed largely from those in rainbow trout, carp, and catfish (241). 

After a single oral or intravenous administration of tetracycline to chickens at dosage rates of 100 mg/kg or 20 mg/kg bw, respectively, residue concentrations in muscle, kidney, and liver tissues were 0.03, 0.13, and 0.05 ppm, respectively, at 5 days posttreatment (248). Following intramuscular injection of tetracycline and oxytetracycline to goats at a dosage of 15 mg/kg bw at 24 h intervals for 4 days, residual levels of both drugs could be found in milk by day 4 after the last administration (249). The concentration of tetracycline at this time was 0.913 ppm, while that of oxytetracycline was 0.459 ppm in the milk. 

After subcutaneous or intramuscular injection of netobimin into cattle, absorption was rapid but plasma levels of radioactivity were lower than those achieved following oral administration. This indicates that absorption occurred prior to the conversion to albendazole since high levels of parent drug were found in plasma and milk soon after the injection. On the other hand, at 12 h after the injection the parent drug could not be detected at the injection site or in liver. 

Residue depletion studies (60) in swine given a single intramuscular injection of doramectin at a dosage of 375 mg/kg bw showed that residues of the parent drug were always higher at the injection site and declined from 9000 ppb at 7 days after treatment to 70 ppb at 35 days after treatment. Residues in back fat declined from 470 ppb at 7 days after treatment to 50 ppb at 35 days after treatment. Residues in liver declined from 160 ppb at 7 days after treatment to IS ppb at 35 days after treatment. Residues in kidney and muscle declined from so and 40 ppb, respectively, at 7 days after treatment to 18 and 11 ppb, respectively, at 21 days after treatment. 

Residue depletion studies in lactating cattle given a single intramuscular injection of 1 g betamethasone/kg bw showed that the concentrations of the parent drug in milk were in the range 3.82-38.22 nmol/L at the first milking, and lower than 1.6 ppb at the seventh milking. 

Following oral administration of radiolabeled furosemide, excretion was reported to be almost complete within 3 days in rats (96-98%) and dogs (98-99%). Rat urine contained 40-50% of the parent drug, 30% 4-chloro-5-sulfamoyl-anthranilic acid, and four unidentified metabolites that accounted for the rest of the administered radioactivity. In contrast, urine of dog and monkey contained 85% unmetabolized furosemide, 7% 4-chloro-5-sulfamoyl-anthranilic acid, and the remainder was due to unidentified metabolites. Following intramuscular injection of 5 mg furosemide/kg bw in cattle, the half-life for plasma elimination was estimated at 4.3 h. In contrast, the half-life of furosemide in cattle was reported to be less than 1 h following intravenous administration. 

Following intramuscular injection of 0.5 mg propiopromazine/kg bw in swine, the parent drug decreased in kidney from 215 to 53 ppb between 2 and 24 h postdosing, although not in the liver where it remained at about 200 ppb. The concentrations of propiopromazine at the injection site also decreased with time, being 22, 19, and 6 ppm at 2, 8, and 24 h, respectively (103). 

The persistence of residues at intramuscular injection sites may be due in part to the irritant response produced in the muscle (52). Chloramphenicol, tylosin, penicillins, dihydrostreptomycin, and oxytetracycline have been shown to produce local irritation at the site of injection, leading to residue persistence this may be exacerbated by the solvent used. However, residues do not persist with proper injection of drugs and use of formulations that do not cause severe irritation (52), as has been demonstrated with one oxytetracycline product that produced little irritation (53-55). 

Ovarian hyperstimulation syndrome occurred in a woman with polycystic ovarian syndrome, 3 weeks after an intramuscular injection of leuprorelin acetate for endometriosis (68). She was later given further courses of the drug without this complication. 

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