Intramuscular dose, excretion

Antimonials are irritating to the intestinal mucosa and therefore are administered by intramuscular or slow intravenous injection. Peak blood concentrations occur in 2 hours. These drugs bind to cells, including erythrocytes, and are found in high concentrations in the liver and spleen. As compared with the trivalent antimonials, which are no longer used, the pentavalent antimonials bind to tissue less strongly. This results in higher blood levels, more rapid excretion, and lowered toxicity. Pentavalent antimonials are rapidly excreted in the urine, with up to one-half of the administered dose excreted in 24 hours. 

Disposition in the Body. About 30% of an oral dose is absorbed, the remainder being inactivated by gastric acid maximum concentrations are attained about 1 hour after oral administration. After intramuscular injection it is rapidly absorbed, peak concentrations being attained in 15 to 30 minutes. About 60 to 90% of an intramuscular dose is excreted in the urine, mainly in the first few hours the urinary material consists of unchanged drug and penicilloic acid (about 20% of the dose). Biliary excretion also occurs. 

Disposition in the Body. Poorly absorbed after oral administration. Less than 5% of an oral dose is excreted in the urine in 24 hours, compared to 50% of an intramuscular dose. 

Disposition in the Body. The hydrochloride is well absorbed after oral administration the decanoate and enanthate are slowly absorbed from sites of injection. Fluphenazine is metabolised by sulphoxidation, hydroxylation, and conjugation with glucuronic acid or sulphate. Fluphenazine sulphoxide and 7-hydroxy-fluphenazine have been detected in urine and faeces. After an oral dose of the hydrochloride, 20% is excreted in the urine and 60% is eliminated in the faeces in 7 days after an intramuscular dose of the enanthate, 26% is eliminated in the faeces and 14% excreted in the urine in 14 days after an intramuscular dose of the decanoate, 17% is eliminated in the faeces and 6% excreted in the urine in 30 days. 

The purpose of the rarely used Schilling urinary excretion test is to diagnose vitamin B12 deficiency anemia caused by a B12 absorption defect resulting from a lack of intrinsic factor (pernicious anemia). The patient first receives an oral dose of radiolabeled vitamin B12. Two hours later, the patient receives a large intramuscular dose of nonlabeled vitamin B12 to saturate plasma transport proteins. Any excess vitamin B12 that is not taken up by the transport proteins or stored in the liver will be excreted in the urine. A 24-hour urine collection is then measured for radioactivity. If sufficient gastrointestinal intrinsic factor is being produced, the radiolabeled B12 will be absorbed. 

EXCRETION Normally, penicilhn G is ehminated rapidly from the body, mainly by the kidney. Approximately 60-90% of an intramuscular dose of penicilhn G in aqueous solution is ehminated in the urine, largely within the first hour after injection. The remainder is metabolized to penicilloic acid. The tj j for elimination of penicilhn G is 30 minutes in normal adults. Approximately 10% of the drug is ehminated by glomerular filtration and 90% by tubular secretion. 

Because IFNs induce long-lasting cellular effects, their activities are poorly predicted from usual pharmacokinetic measures. After intravenous dosing, clearance of IFN from plasma occurs in a complex manner. With subcutaneous or intramuscular dosing, the plasma elimination t of IFN-a ranges from 3 to 8 hours, largely due to distribution to the tissues, cellular uptake, and catabolism in the kidney and liver. Negligible amounts are excreted in the urine. Clearance of IFN-a is reduced by 7Wc in dialysis patients. 

For chronic iron intoxication e.g., thalassemia), an intramuscular dose of 0.5-1.0 g/day is recommended, although continuous subcutaneous administration (1-2 g/day) is almost as effective as intravenous administration. When blood is being transfused to patients with thalassemia, 2 g deferoxamine (per unit of blood) should be given by slow intravenous infusion (rate not to exceed 15 mg/kg/h) during the transfusion but not by the same intravenous fine. Deferoxamine is not recommended in primary hemochromatosis phlebotomy is the treatment of choice. Deferoxamine also has been used for the chelation of aluminum in dialysis patients. Deferoxamine is metabohzed principally by plasma enzymes, but the pathways have not been defined. The drug also is excreted readily in the urine. 

In 10 healthy subjects the urinary excretion of a 100-mg dose of nitrofurantoin was approximately halved by pretreatment with a 10-mg intramuscular dose of metoclopramide and a 10 mg oral dose of metoclopramide given 30 minutes before the nitrofurantoin. ... 

The percents of the total dose excreted In urine over the 10 days averaged (high and low dose) dlmethoate, 12% dlchlorvos, 10% ronnel, 11% dlchlofenthlon, 57% carbophenothlon, 66% parathlon, 40% and leptophos, 50%. Very little of this excretion occurred beyond the third day post exposure. Intact residues of ronnel, dlchlofenthlon, carbophenothlon, and leptophos were found In fat on day 3 and day 8 post exposure. In another rat experiment, animals were dosed once dermally and Intramuscularly with azlnphosmethyl (44). About 78% of the dermal dose had been excreted In urine In 24 hr. Its rate of excretion peaked In 8-16 hr., continued at about the same rate for another 16 hr., and declined to a steady level 16 hr. thereafter. There was a linear relationship between dermal dose and urinary excretion. The Intramuscular dose was excreted much more rapidly than the dermal dose. No apparent relationship existed between the Intramuscular dose and urinary excretion. 

Because these experiments illustrate the excretion differences between dermal. Intramuscular, and oral dose excretion, the excretion differences between compounds, and also problems about which urinary metabolite to monitor (see 44). a very comprehensive experimental design would be necessary to correctly model dermal exposure, absorption, and urinary metabolite levels. Statistical problems, centering around replicate variation and the resulting necessity for abnormally large numbers of replications, could drive the costs of such an experiment In small animals, and certainly in humans, to prohibitively high levels. 

Ceftazidime was dosed intramuscularly and intravenously to human volunteers (Table XII). Peak serum concentrations of 10, 23, and 27 p,g/ ml were obtained after intramuscular doses of 0.25, 0.5, and 0.75 g. The plasma half-life varied from 1.4 hr for the low dose to 1.8 hr for the high dose. Serum concentrations of 8 p,g/ml were still present 1.5 (0.25 g dose), 4.2 (0.5 g dose), and 6.1 hr (0.75 g dose) after intramuscular administration. Urinary recovery of ceftazidime varied from 48 to 88% in 88% in humans. Serum levels of 61 fig/ml were measured immediately after intravenous administration of 0.5 g of ceftazidime to human volunteers. Preliminary experiments indicated that concomitant administration of probenecid had no effect on the rate of excretion of ceftazidime. This indicates that ceftazidime is excreted by glomerular filtration and not by tubular secretion. 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

The ability of the liver to act as a depot for vitamin Bi2 (B28, G13) enables us to use this vitamin as an index of proper hepatic function. Hepatic disorders lead to an increased Bi2-binding in the serum (J5, R3), suggesting that the blood assumes a greater role in the conservation of B12. We have reported that patients with liver disease excreted invariably less than 10 fig of Bi2> 8 hours after a 50-[ig intramuscular load dose of the vitamin. In contrast, normal subjects excreted 24-40 pg, i.e., 50-80% of the vitamin in the same test (B14). These results were correlated with various chemical determinations indicative of hepatic disorders (Bl). In Table 16 the clinical diagnosis and the various liver-... 

Salbutamol may be administered parenterally as an intravenous infusion at 3-20 pg min-1 with the dose being titrated to therapeutic effect. Side effects notably tachycardia are more common with parenteral or nebulised formulations. The drug may also be administered by the subcutaneous or intramuscular routes. Salbutamol is conjugated in the liver and excreted both in the urine as unchanged drug and metabolites, and also in the faeces. 

Cefazolin is the only first-generation parenteral cephalosporin still in general use. After an intravenous infusion of 1 g, the peak level of cefazolin is 90-120 mcg/mL. The usual intravenous dosage of cefazolin for adults is 0.5-2 g intravenously every 8 hours. Cefazolin can also be administered intramuscularly. Excretion is via the kidney, and dose adjustments must be made for impaired renal function. 

Aminoglycosides are absorbed very poorly from the intact gastrointestinal tract almost the entire oral dose is excreted in feces after oral administration. However, the drugs may be absorbed if ulcerations are present. After intramuscular injection, aminoglycosides are well absorbed, giving peak concentrations in blood within 30-90 minutes. Aminoglycosides are usually administered intravenously as a 30- to 60-minute infusion after a brief distribution phase, this results in serum concentrations that are identical with those following intramuscular injection. 

The absorption of spectinomycin is poor via the oral route, but rapid and extensive after intramuscular injection. It is not extensively metabolized in animals and rapidly excreted in the urine (16). Following subcutaneous injections of spectinomycin sulfate to cattle, 70-83% of the dose was excreted in the urine and 62-64% of this was parent spectinomycin (17). Several minor metabolites were found in the urine that consisted mostly of dihydroxyspectinomycin and two acetylated isomers, and an unusual ammoniated spectinomycin metabolite and its acetylated derivative. There was also some evidence, but it was not compelling, for a spectinomycin sulfate conjugate. Dihydrospectinomycin and parent spectinomycin were the only identifiable major components found in the liver and the kidney, respectively. Liver and kidney retained the highest concentrations of total residues throughout the 15-day withdrawal period. 

Results of pharmacokinetic studies of streptomycin are in most cases also applicable to dihydrostreptomycin and vice versa. In animals, the absorption of both streptomycin and dihydrostreptomycin is poor via the oral route but rapid after intramuscular administration. In cattle, peak serum levels were obtained 1 h after intramuscular injection of either streptomycin or dihydrostreptomycin (18), whereas serum concentrations produced in sheep and horses paralleled those obtained in cattle (19). As a result, most of an oral dose is recovered in the feces whereas most of a parenteral dose is recovered in the urine. However, if kidney function is severely impaired, little of an intramuscularly administered dose is excreted in the urine. 

Amoxicillin is widely distributed in body tissues and its metabolism is limited. Excretion of amoxicillin is tlirough the kidney, resulting in high concentrations in both the kidney tissue and urine, where the levels may be 100-fold higher than that in serum. Concentrations in milk are 10 times lower than those in serum. Following intramuscular or subcutaneous injection to goats, levels of amoxicillin in milk were very close to the detection limit of 10 ppb within 24 h after the last dose (65). 

In dogs, absorption following oral administration tends to be poor. At similar oral doses, peak serum levels are lower and plasma levels are less persistent than those observed for methicillin. Following intramuscular administration, however, maximum concentrations in serum are reached within 30 min. In contrast to methicillin, liver is the main excretory pathway for nafcillin. Like most other penicillins, nafcillin undergoes biotransformation to a small extent. Parent compound and its metabolites are excreted in bile and urine. Concentrations of nafcillin in tissues tend to be higher and more persistent following parenteral administration than was the case for methicillin, obviously due to enterohepatic recirculation. 

Ceftiofiir is absorbed poorly after oral administration but rapidly after intramuscular injection. In all species, ceftiofur was rapidly metabolized to desfuroyl-ceftioftir and fiiroic acid. Desfiiroylceftiofur occurred in the free form in the plasma of treated cattle but was covalently bound to plasma proteins in rats (82). Maximum blood concentrations of ceftiofiir-related residues were achieved within 0.5 and 2 h of dosing. Unmetabolized ceftiofur was generally undetectable in blood within 2-4 h of dosing (83). More than 90% of the administered dose was excreted within 24 h of administration, mostly in urine. Residues in urine and feces were composed primarily of desfiiroylceftiofur and desfiiroylceftiofur cysteine disulfide, with small amounts of unmetabolized ceftiofur. 

In general, the macrolides are administered orally but sometimes also paren-terally. All the members of this group are well absorbed and are distributed extensively in tissues, especially in the lungs, liver, and kidneys, with high tissue to plasma ratios. They are retained in the tissues for long periods after the levels in the blood have ceased to be detectable. Elimination of all macrolides occurs primarily through hepatic metabolism, which accounts for approximately 60% of an administered intravenous dose the remainder is excreted in active form in the urine and bile. With oral and intramuscular administration, urinary excretion decreases, but biliary excretion and hepatic metabolism increase proportionally. Milk has often macrolide concentrations severalfold greater than in plasma (7). 

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. 

Following either oral or parenteral administration, levamisole is rapidly absorbed, but the parenteral route produces higher blood levels (6). When given intramuscularly, peak plasma levels are almost twice those attained by oral administration of the same dose. After subcutaneous administration, peak plasma levels of levamisole occur within 30 min, with 90% of the total dose being excreted in 24 h, mainly in the urine. 

Following intramuscular administration to sheep of 1 mg xylazine/kg bw, two-thirds of the injected dose could be absorbed within 10 min (113). The drug was rapidly distributed to different tissues, and rapidly eliminated. The rapid elimination of xylazine in sheep is probably related to its intense metabolism rather than to its rapid renal excretion. This hypothesis was supported by the lack of significant amounts of the intact drug in urine samples collected every 10 min from treated sheep. 

Tramadol is available as drops, capsules, and sustained-release formulations for oral use, suppositories for rectal use, and solution for intramuscular, intravenous, and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 h, reach peak concentrations after 4.9 h, and have a bioavailability of 87 to 95% compared with capsules. One 100-mg dose given to healthy volunteers resulted in plasma levels of 375 ng/ml at 1.5 h.55 Tramadol is 20% bound to plasma protein and it is rapidly distributed in the body it is mainly metabolized by O- and A-demethylation forming glucuronides and sulfates that are excreted by the kidney. 

---