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The time course of action of (-)-hyoscine after intramuscular injection.

1. Although (-)-hyoscine has been in clinical use for many years, there is little detailed information concerning the speed of absorption or duration of action of the drug after single intramuscular doses.2. The time course of action of the drug was therefore examined using biological methods, and measurements were made of saliva flow, pulse rate, pupil diameter and mental alertness for up to 8 hr after doses of 0.4, 0.2, 0.1 and 0.05 mg of the hydrobromide.3. These techniques gave comparable results and peak activity was achieved at 1-2 hr after dose and followed by a gradual decline over the 8 hr period.4. The results are compared with those of earlier experiments of a similar kind, and discussed in relation to their bearing on both therapeutics and experimental design.

Absorption↗

Evaluation of testosterone response to intramuscular injection of GnRH and its correlation with sperm quality parameters in cockerels.

Eight 40-week-old New Hampshire cockerels (average liveweight: 3.10 +/- 0.2 kg) were used for studying the testosterone response to a single intramuscular dose (5 micrograms/kg b.w.) of exogenous 6D-Phe gonadotropin releasing hormone (GnRH). Serum samples were collected at 15-min intervals during the first hour and at half-hour intervals up to two hours post injection. The semen samples were collected 24 h before GnRH treatment. Testosterone peaks were found 45 to 60 min after the treatment. The coefficient of correlation between the semen quality parameters and the testosterone response to GnRH was evaluated both by Rank correlation and by multiple regression analyses. Rank correlation showed moderate but not significant values while multiple regression analyses showed a close correlation (multiple R = 0.72). The results show that testosterone response to GnRH may be used as a marker of semen quality in cockerels.

Animals↗

Systemic effect of human growth hormone after intramuscular injection of a single dose of a muscle-specific gene medicine.

A muscle-specific gene medicine is described that provides for long-term secretion of biologically active human growth hormone (hGH) from skeletal muscle into the systemic circulation. The hGH gene medicine is composed of a muscle-specific hGH plasmid expression system complexed with a protective, interactive, non-condensing (PINC) delivery system. The muscle-specific gene expression system, pSK-hGH-GH, was constructed by linking the promoter/enhancer regions of chicken skeletal alpha-actin to hGH gene. C2C12 myoblast transfection with pSK-hGH-GH resulted in the synthesis of hGH in a muscle-specific manner. Direct injection into rat tibialis cranialis muscle of pSK-hGH-GH complexed with a polymeric PINC delivery system, polyvinylpyrrolidone (PVP), produced hGH levels in muscle that were 10- to 15-fold higher compared with plasmid formulated in saline at 14 days post-injection. Intratracheal instillation in rat lung of pSK-hGH-GH did not produce significantly detectable levels of hGH. In hypophysectomized rats, a single intramuscular dose of the pSK-hGH-GH/PVP complex resulted in hGH expression and a subsequent increase in serum levels of rat IGF-I and growth. hGH expression and effects on rat serum IGF-I levels were detectable up to 28 days after injection of formulated plasmid and effects on growth were detectable unto 21 days. Anti-hGH antibodies were detectable in serum at 14 days post-injection, reached a plateau at 21 days, and remained elevated through the study period. Cyclosporin treatment of the pSK-hGH-GH/PVP-injected animals completely inhibited the antibody response and resulted in increased hGH expression.

Actins↗

Concentrations of methicillin in blood, normal milk and mastitic milk of cows after intramuscular injection of methicillin and tamethicillin.

Tamethicillin (TAM) is a basic ester pro-drug of methicillin (MET) which is converted in the body by non-specific esterases to MET. Equal doses of MET and TAM were administered intramuscularly in a crossover trial involving four dairy cows. Acute mastitis was induced in each cow by infusing two quarters of the udder with Escherichia coli endotoxin 3 h before antibiotic administration. Peak serum MET concentrations after MET injection were significantly (P less than 0.001) higher than peak serum drug concentrations after TAM injection. The t1/2 of MET in serum after MET and TAM treatments were 18 min and 2 h, respectively. Normal milk MET concentrations during the first 8 h after TAM administration were significantly (P less than 0.05) higher than after MET treatment. Mastitic milk MET concentrations during the period 2-6 after MET injection were significantly (P less than 0.01) higher than after TAM administration. However, MET concentrations which were equal to or higher than the minimal inhibitory concentrations for penicillin G-resistant staphylococci were maintained in the mastitic milk for 8 h after treatment with MET and TAM.

Animals↗

A randomized double-blind, placebo-controlled trial of the EMLA patch for the reduction of pain associated with intramuscular injection in four to six-year-old children.

UNLABELLED: The effectiveness of a eutectic mixture lidocaine-prilocaine topical anaesthetic cream (EMLA) patch compared with a placebo patch in the reduction of pain associated with intramuscular immunization was evaluated. As part of the study, 161 children (aged 4-6-y) undergoing routine diphtheria, pertussis, tetanus and polio (DPTP) immunization in five urban and five rural private office settings were randomly assigned to an EMLA patch (n = 83) or a placebo patch control group (n = 78). Pain measurements included: child's self-report on a Faces Pain Scale; facial action on the Child Facial Coding System; the Children's Hospital of Eastern Ontario Pain Scale and parent and technician ratings on a Visual Analogue Scale. Parents also rated their own and their child's immunization-related anxiety on a Visual Analogue Scale. The EMLA patch group had significantly less pain on all four pain measures compared with the placebo group. Of the children in the placebo group, 43% had clinically significant pain, compared with 17% of children in the EMLA patch group. No severe adverse symptoms occurred as a result of either EMLA or placebo patch application. CONCLUSION: The EMLA patch reduced immunization pain in 4 to 6-y-old children during needle injection.

Anesthetics, Combined↗

Intramuscular injections through indwelling cannulae.

A study was performed to establish the feasibility of an indwelling intramuscular cannula for the administration of post-operative analgesic and anti-emetic medication. One-hundred cannulae were inserted for periods up to 7 days (mean = 2.4). A mean of five and maximum of 15 injections were made through each cannula with a maximum volume in any patient of 29 ml. On 18 occasions cannulae were removed for minor complications; no serious complications were seen. This technique may be useful for administration of intramuscular analgesic and anti-emetic medications in the post-operative period.

Adolescent↗

Severe complication to phytomenadione after intramuscular injection in woman in labor. Case report and review of literature.

A 28-year-old woman in labor developed a severe anaphylactoid reaction, necessitating acute cesarean section, with subsequent neonatal death, after receiving 10 mg of phytomenadione (Konakion) by the intramuscular route. Allergologic investigations revealed no type I reaction against the drug, and the symptoms were considered to be caused by drug-induced intolerance. Prophylactic administration of phytomenadione to the infant rather than to the parturient is recommended.

Adult↗

Appearance of pethidine and norpethidine in cerebrospinal fluid of man following intramuscular injection of pethidine.

The plasma and cerebrospinal fluid (CSF) concentrations of pethidine and its main metabolite in plasma, norpethidine, were determined in 20 patients undergoing minor surgery who had received pethidine chloride as premedication in a standard dose of 100 mg intramuscularly. The disposition of pethidine and norpethidine in plasma was followed for 3-8 h after administration. The rate of transfer of the drug and its metabolite from plasma to CSF was assessed on the basis of a single sample of CSF taken from each patient. Pethidine appeared within less than 18 min in the CSF, reaching a maximum after about 90 min. After that, the pethidine concentration ratio CSF/plasma was relatively stable at 0.4-0.5. This is in agreement with the concept that the concentration of a drug in CSF is correlated with the concentration of unbound drug in plasma at equilibrium. Norpethidine which was present in rapidly increasing concentrations in plasma after a delay of 30 min, appeared in CSF in a slower and more erratic fashion as compared to the parent compound. However, after 240 min, the CSF/plasma concentration ratio was similar for pethidine and norpethidine. Thus, transfer from plasma to CSF occurs relatively rapidly. There is little evidence for a functionally significant blood-brain barrier for pethidine and norpethidine.

Adult↗

Fixed combination mezlocillin/oxacillin injected intramuscularly. Comparative study of local tolerability compared with ampicillin and determination of effectiveness and tolerability in the treatment of surgical and urinary tract infections.

The results of two studies on tolerability and efficacy of mezlocillin/oxacillin are reported. The pain caused by i.m. injection of 1 g (20% solution) of the fixed antibiotics combination mezlocillin/oxacillin is compared with that caused by 1 g ampicillin. The injection volume was 5 ml. The statistical analysis of the patients' statements indicates a better tolerance of the fixed antibiotics combination mezlocillin/oxacillin than of ampicillin. The second study was determined the clinical efficacy and tolerability of mezlocillin/oxacillin in the treatment of wound infections, biliary tract infections, urinary tract infections, appendicitis and peritonitis. 19/20 patients were clinically cured after about 7 days o treatment with i.m. injections of 1.5 g mezlocillin/oxacillin in 6 ml of a 25% aqueous solution t.i.d. Treatment had to be discontinued after 3 days in one case because of a generalized exanthema. No other side effects were reported. These studies show that both the i.m. injection o the 20% solution of 1 g mezlocillin/oxacillin combination and the 25% solution of 1.5 g of this combination are tolerated without problems.

Adolescent↗

Ceftriaxone therapy of bacterial meningitis: cerebrospinal fluid concentrations and bactericidal activity after intramuscular injection in children treated with dexamethasone.

Antibiotic therapy is administered intravenously to children with bacterial meningitis to achieve the highest possible blood and cerebrospinal fluid (CSF) concentrations. However, intravenous access for the entire duration of therapy may be difficult in some children. Intramuscular therapy offers a more versatile option; however, CSF concentrations and bactericidal activity following im injection in children concurrently treated with dexamethasone have not been studied. We prospectively evaluated 37 children given an im dose of ceftriaxone on either the 3rd, 6th or 9th day of antibiotic therapy while receiving dexamethasone for the first 4 days of treatment. All children were required to have normal peripheral perfusion at the time of im injection. Four to 6 hours after im injection CSF was obtained. The average age of study patients was 28 months; Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b were responsible for 95% of all infections. All children studied had detectable CSF ceftriaxone concentrations, with mean (+/- SD) concentrations (microgram/ml) on Days 3, 6 and 9 of therapy of 5.7 +/- 5.5 (n = 12), 5.2 +/- 5.0 (n = 14) and 2.0 +/- 2.6 (n = 10), respectively. All CSF bactericidal titers for N. meningitidis, S. pneumoniae and H. influenzae type b, regardless of day of im injection, were > or = 1:64. Intramuscular ceftriaxone therapy of bacterial meningitis may be a reasonable therapeutic option for the convalescing child with good peripheral perfusion.

Ceftriaxone↗

Depletion of intramuscularly injected ceftiofur from the milk of dairy cattle.

Ceftiofur sodium, a new broad-spectrum cephalosporin, has been approved in the US, Canada, and several other countries throughout the world to treat bovine respiratory disease in cattle and dairy cows. In Experiment 1, 6 lactating cows were intramuscularly treated with 2.29 mg of [14C]ceftiofur/kg of BW daily for 5 d. In Experiment 2, 30 additional cows at three locations were similarly treated with 2.2 mg of ceftiofur (unlabeled)/kg of BW. Milk was collected every 12 and 24 h after each dose and every 12 h up to 5 d after the last dose. The majority of milk samples, both during treatment (12 and 24 h after each dose) and after the last dose (up to 5 d following ceftiofur treatment), were negative by screening procedures based on microbial inhibition (Delvotest-P, Bacillus stearothermophilus disk assay, and cylinder plate assays). The receptor-binding Charm Test II assay, which has a limit of detection of .005 ppm of ceftiofur, gave positive tests for milk samples up to 48 h following treatment. When the Charm Test II assay is used with .008 IU/ml of penicillin as a positive control, 44% of the samples from individual cows were negative at 12 h posttreatment. Ninety percent of the samples from individual cows were negative at 24 h after the last treatment. The use of ceftiofur in dairy cattle in accordance with the label directions does not result in total residues in milk higher than the FDA-calculated safe concentration of 1-ppm ceftiofur equivalents. The milk from individual cows did not test positive by the commercial screening assays examined in this study, except for the Charm Test II. The Charm Test II was 90% negative using the Charm Sciences criteria at 24 h after the last treatment.

Animals↗

Pharmacokinetics and tissue residues in channel catfish, Ictalurus punctatus, given intracardiac and intramuscular injections of gentamicin sulfate.

We studied the rate of absorption, distribution and elimination of gentamicin sulfate in the channel catfish, Ictalurus punctatus. It was determined that the plasma half-life of immunoreactive gentamicin was 12 to 15 hours in the catfish and the rate of elimination from fish after intracardiac and intramuscular (im) routes are not significantly different. Compared to mammals, the very extended half-life is probably the result of a greater unionized fraction of drug in the central compartment and increased reabsorption of drug from the alkaline urine of the fish. Tissue levels at the end of one dose experiments approximate what was predicted based on the intracardiac microconstants. A dosage regimen was established on a 24 hr interval that would keep peak plasma concentration between 10-13 micrograms/ml and allow trough concentrations of 3-4 micrograms/ml. Intramuscular gentamicin appears to have a bioavailability of approximately 37%. Finally, a renal lesion was produced by giving gentamicin im at 10 mg/kg every 33 hr for 6 treatments. The lesion was identical to that described for other mammals and was reversible even while medication was continued.

Animals↗

Treatment of gonococcal infections with a single 250 mg intramuscular injection of trospectomycin sulphate vs ceftriaxone sodium.

Trospectomycin sulphate is a new, more potent analog of spectinomycin, which is active in vitro against penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. This study was designed to determine the bacteriologic and clinical efficacy as well as safety of a single intramuscularly administered 250 mg dose of trospectomycin sulphate in the treatment of uncomplicated gonorrhoea (cervical, urethral, pharyngeal and anal). Ceftriaxone sodium was used as a comparator antibiotic in a single 250 mg intramuscular dose. Seventy-four patients (36 women and 38 men) were evaluable in the trospectomycin treated group and 40 patients (22 women and 18 men) in the ceftriaxone treated group. The overall bacteriologic cure rate was 98.6% (73/74) for trospectomycin and 95% (38/40) for ceftriaxone. Bacteriologic failures were observed among women 1/36 (2.8%) treated with trospectomycin and 2/22 (9.1%) treated with ceftriaxone. The overall clinical success rate (clinically cured plus clinically improved) was 90.5% for trospectomycin and 100% for ceftriaxone. Adverse events were reported rarely in both groups. Less than 10% of patients complained of pain and/or tenderness at the injection site for both drugs; one patient developed a generalized, pruritic rash which occurred three days after administration of trospectomycin and resolved within six days. In conclusion, a single dose of 250 mg i.m. trospectomycin appears to be at least as effective and safe as a single dose of ceftriaxone in the treatment of uncomplicated gonorrhoea.

Adolescent↗

Efficacy of streptococcal preparation OK-432 for gastric cancer patients--comparison between intradermal and intramuscular injection.

Nonspecific immunotherapy with OK-432, penicillin and heat treated lyophilized powder of Su-strain of streptococcus pyogens A3, was evaluated in patients with recurrent or unresectable stomach cancer to assess the relative benefit of the preparation administered by different routes. Comparative studies were made of the variation in immunological parameters, the survival rate and the incidence of adverse reactions in two groups of patients with uniform background factors: 24 receiving the preparation intradermally and 18 receiving intramuscular doses of the preparation. In for former group, no serious adverse reaction occurred but more marked improvement was achieved in various immunological parameters examined. The survival rate was significantly higher (P = 0.005) for patients receiving intradermal than those receiving intramuscular doses of the preparation. The results of the present study showed that the preparation is of greater value when it is administered intradermally than intramuscularly.

Adult↗

Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon alfa-2a by intramuscular injection.

More than 1600 patients with neoplastic disorders have received recombinant human interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) as part of ongoing or completed clinical trials. In this report, the efficacy of interferon alfa-2a therapy was compared with the incidence of antibodies to this interferon in 617 patients who received the drug by intramuscular administration. Antibody measurements were performed using a highly sensitive enzyme immunoassay, and an interferon antiviral neutralization bioassay. Partial or complete remission occurred in 28% (43 of 152) of the antibody-positive patients, and in 24% (112 of 465) of the antibody-negative patients (P = 0.33). The highest incidence of antibody formation occurred among patients with renal cell carcinoma and acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (44% and 34%, respectively). Both the duration of treatment and length of survival were significantly longer for antibody-positive than for antibody-negative patients. No significant intergroup differences emerged for response rates or for time to onset or duration of therapeutic response. When results from the above assays were compared to those used for the detection of antibodies to recombinant interferon alfa-2b (Intron A, Schering-Plough Inc., Kenilworth, NJ), the immunoradiometric assay method was determined to be seriously deficient for determination of antibody incidence. This decreased assay sensitivity may account for the reportedly lower incidence of antibodies to recombinant alfa-2b interferon.

AIDS-Related Opportunistic Infections↗

Inhibition of tumor growth by intramuscular injection of cDNA encoding tumor necrosis factor alpha coupled to NGR and RGD tumor-homing peptides.

The antitumor properties of tumor necrosis factor alpha (TNF) and its efficacy in selective destruction of tumor-associated vessels are well known. Besides the TNF protein, the TNF gene has been used for gene therapy of cancer and shown to induce antitumor responses both in animal models and in patients. We show here that the therapeutic properties of the TNF gene are improved by fusing the TNF sequence with those of peptides able to target tumor vessels, such as CNGRCG or ACDCRGDCFCG. Intramuscular administration of plasmid DNA encoding CNGRCG-TNF and ACDCRGDCFCG-TNF (pNGR-TNF and pRGD-TNF, respectively), but not plasmids encoding TNF (pTNF) or empty vector (pMock), inhibited the growth of subcutaneous murine B16F1 melanomas and RMA-T lymphomas implanted at sites distant from the site of plasmid injection. The combination of pNGR-TNF or pRGD-TNF with doxorubicin or melphalan induced stronger effects than single agents. These treatments induced antitumor effects without activating toxic or negative feedback mechanisms. In addition, pRGD-TNF increased the uptake of an antibody directed to a tumor-associated antigen. These results suggest that the therapeutic properties of NGR-TNF and RGD-TNF cDNAs are greater than those of TNF cDNA and provide the rationale for developing new gene therapy approaches based on vascular targeting with TNF coupled to tumor-homing peptides.

Animals↗