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`(30 mg) and single intramuscular injections ofsodium
`phenobarbital (equivalent to 27.4 mg phenobarbital).
`Bars indicate one standard error (n = 5). Reproduced.
`by permission. from J. Clin. Pharmacol. 18. 100—105
`([978).
`
`509.1111 glut-at may
`
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`‘
`
`Figure 7—Injet'tion site in gluteus muscle. Thisjlg‘ure.
`and also Figures 8, 9, and I0, are reproduced by per-
`mission from R. D. M urser and J. J. O'Neill. Phar-
`macology and Therapeutics. 4!]: ed. Macmillan. New
`York. N I", l 97 i.
`
`is often used to administer drugs that are
`poorly absorbed from the gastrointestinal
`tract. For example. piperacillin. a new semi-
`synthetic aminobenzyl penicillin derivative
`which is poorly absorbed orally. is rapidly and
`reliably absorbed after intramuscular ad-
`ministration (10).
`However, drugs are not always completely
`available following intramuscular injection.
`Slow or incomplete absorption from intra-
`muscular sites has been reported for chlordi-
`azepoxide. diazepam, digoxin, phenytoin, and
`phenobarbital, and the extent of absorption
`may also be influenced by the patient's age.
`Although phenobarbital appears to be com-
`pletely bioavailable following intramuscular
`injection to children. it is only 80% available
`compared to oral doses in adults (1 1). Serum
`levels of phenobarbital obtained during 21
`days following oral and intramuscular doses
`are shown in Figure 6. Note the very long du—
`ration of this drug in serum from both dosage
`routes. The biological half-life of phenobar-
`bital from these data was approximately 90
`hours.
`
`Intramuscular injections are made deep into
`the skeletal muscles. preferably far away from
`major nerves and blood vessels. In adults. the
`upper portion of the gluteus maximus is a
`frequently used site for this purpose. In infants
`and young children, the deltoid muscles of the
`upper arm or the midlateral muscles of the
`
`thigh are usually preferred. The usual sites for
`
`416
`
`Journal of the Parenteral Drug Association
`
`InnoPharma Exhibit 1094.0009
`
`
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`InnoPharma Exhibit 1094.0010
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`Illa: cm?
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`Gunter hoehonm
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`Figure iii—Anterior glulem‘ injection. The injection site
`is located by placing rmefinger on the illac spine and
`the Ihumh or anotlrerjingerjust below the Hide crux!
`will: the palm nfthe ham! rm the hip. There is Emmi!!-
`erab‘le muscle mass. and no large hlrmd rats/s or "arms;
`in this area.
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`matically in Figures 7—10.
`
`v
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`A
`Aqueous or oleaginous solutions or sus-
`pensions of drugs may be administered intra»
`muscularly. The absorption rates vary widely
`depending on the type of preparation used. as
`
`well as on other biopharmaceutical factors.
`These have been discussed in some detail in a
`review article by Ballard (12).
`Some compounds,
`i.e., penicillins and
`cephalosporins, may cause considerable pain
`when injected intramuscularly and are often
`given
`intravenously whenever possible.
`Cephalothin is particularly painful when given
`intramuscularly and this drug is routinely
`given by the intravenous route.
`The primary factors which influencc the
`
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`luincvimii'n
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`Figure 9~lnjecrimi rile in midamerior region oft/re
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`Figure IOilnjé’t‘lI-UN site in (he (fa/told muscle below
`
`“u, WWW-“nmace”
`
`rate and extent of intramuscular drug ab-
`sorption are summarized in the following
`sections.
`
`Solubility of Drug
`When solutions of sparingly soluble acids
`and bases are injected into the muscle. they are
`gradually buffered to physiological oil. This
`pl-l shift may cause the drug to precipitate at
`the injection site, often resulting in prolonged
`absorption as the precipitated drug slowly
`redissolves in the tissue fluids. An example is
`the precipitation of quinidine base after an
`intramuscular injection of quinidine hydro-
`chloride solution. Precipitation of drug at the
`injection site, and slow resolubilization to yield
`low and possibly undetectable drug levels in
`the bloodstream, may also explain the appar-
`ently incomplete bioavailability of intramus-
`cular phenobarbital and other compounds
`discussed earlier. Clearly,
`the injection of
`larger aqueous fluid volumes will minimize
`drug precipitation at the injection site but
`there are practical limits to the actual volume
`injected, particularly in children.
`
`Solvent Effect
`Drugs Wh‘Ch are poorly water'somblc' c-gW
`dtazepam, can be dissolved in non-aqueous
`
`September-October. 1980. Vol. 34. No. 5
`
`4 l 7
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