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PubMed1999

Pharmacokinetic study of 45Ca administered intravenously following intramuscular injection of vitamin D3 or 25-hydroxyvitamin D3 in early weaned lambs.

The objective of this study was to evaluate the pharmacokinetic parameters of 45Ca administered intravenously at a dose of 50 microCi in young lambs. The experiment was performed on 18 female lambs allocated to three treatments. Six animals received intravenous calcium only; six received intramuscularly vitamin D3 8 days prior to the administration of calcium; and six received intramuscularly 25-hydroxyvitamin D3 5 days prior to the administration of calcium. Blood samples were collected from 15 min up to 8 days after the administration of 45Ca. The different pharmacokinetic parameters (area under the curve, clearance, mean residence time and volume of distribution) were estimated using non-compartmental and compartmental approaches. Statistical analysis of the results showed no significant differences in the pharmacokinetic parameters of the three groups. It can be concluded that vitamin D does not modify either the elimination or the distribution of calcium in the lambs receiving adequate dietary vitamin D.

Animals↗
PubMed1981

Effect of repeated biopsy sampling on endometrial concentrations of sodium benzylpenicillin following intramuscular injection in pony mares.

Endometrial concentrations of sodium benzylpenicillin were determined in biopsy samples from anoestrous pony mares after intramuscular administration of the penicillin at 22,000 iu/kg. Serum samples, collected at the same time as biopsies, were also assayed for their penicillin content. In experiment 1 a single pair of blood and tissue samples was taken from each mare between five and 360 minutes after injection. In experiment 2 each mare was sampled consecutively six times (between five and 300 minutes) after injection. Both serum and endometrial concentration reached a peak between 15 and 30 minutes after injection. Tissue concentrations were lower than serum, except after 180 minutes in experiment 2. This suggests that at the time intervals used in the present study, serial biopsies eventually caused an increase in the endometrial content of penicillin.

Anestrus↗
PubMed1983

Sex differences in the absorption of dapsone after intramuscular injection.

A trial was performed with a long-acting dapsone (DDS) injection, consisting of an aqueous suspension of dapsone crystals, in doses of 900 mg and 1200 mg. Forty-one Ethiopian leprosy patients, 13 women and 28 men, participated in the study. There appeared to be a large discrepancy in the serum concentration curves of dapsone between men and women. Following injection of 900 mg dapsone in men, a peak of 2.28 +/- 1.06 micrograms/ml (mean +/- S.D.) was observed in the first week. After two weeks the serum concentrations had fallen to 0.42 +/- 0.29 micrograms/ml, and after four weeks they fell to 0.11 +/- 0.09 micrograms/ml. Following injection in women, the curves were smooth with a peak in the first week of only 1.04 +/- 0.40 micrograms/ml, while the serum concentrations after four weeks were still 0.42 +/- 0.23 micrograms/ml. The differences between the mean curves of men and women were statistically significant (p less than 0.001). The 1200 mg dapsone injections were only given to men. The explanation of the sex difference in intramuscular absorption can probably be found in the differences in the thickness of gluteal fat in men and women. In these Ethiopian leprosy patients, the non-protein-bound fraction of dapsone comprised 17 +/- 4%. In saliva, 19.5 +/- 7.0% of the dapsone level in serum was found. Methemoglobin levels were raised but did not reach levels of clinical importance. No other significant side effects were observed.

Absorption↗
PubMed2004

Program savings associated with switching testosterone intramuscular injections to topical gel in HIV infected males.

BACKGROUND: HIV-1 infected male patients commonly require testosterone supplementation and intramuscular testosterone (IM) is the most frequently used supplementation method. Currently, the economic burden of testosterone supplementation is borne to a large degree by the clinic providing services to the HIV infected male. Increasingly, clinics are seeking alternative methods to provide supplementation. This analysis describes the economic trade-offs associated with the utilization of topically applied testosterone supplement relative to current supplementation techniques within the clinic setting. METHODS: Twenty-three patients that had been receiving IM were switched to topical testosterone gel (TOP). A 1-month time-and-motion study, identification of IM administration specific supplies, and costs for acquisition and disposal of these supplies were conducted or gathered to quantify costs of providing bi-weekly IM to patients. The analysis describes potential resource savings by switching 23 HIV patients served in a safety-net provider setting from IM to TOP. The analysis considers both a pre and post-evaluation period whereby patients received IM in the pre-evaluation period and then were switched to TOP in the follow-up period. Economic assessments considered direct medical costs for the preparation and administration of the product but did not incorporate other outcomes in the analyses. RESULTS: Only one of 23 patients switched experienced recurrence of symptoms and no patients developed adverse effects associated with the switch. In contrast, substantial resources could be realized with the utilization of the topically applied testosterone relative to the injectable formulations with approximately $80,938 fewer dollars spent on provision of IM. CONCLUSIONS: Switching patients from IM to TOP resulted in no deleterious affects and is estimated to have saved the clinic considerable resources, even if TOP had to be provided by the clinic.

Administration, Cutaneous↗
PubMed2005

High performance liquid chromatographic analysis an pharmacokinetic characteristics of ID-7181, a novel quaternary ammoniopropenyl cephalosporin, following intravenous and intramuscular injections to rats.

The purpose of the present study was to examine the pharmacokinetic characteristics of 7-[(z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[(E)-3-(E)-(1-carbamoyl-1-propene-3-yl) 3-ethylmethylammonio]-1-propene- 1-yl]-3-cepheme-4-carboxylate (CAS 206126-08-1, ID-7181), a novel quaternary ammoniopropenyl cephalosporin that contains two vinyl groups at the C-3 side chain, after being administered intravenously (i.v.) or intramuscularly (i.m.) to rats. An HPLC-based method was developed to analyze the ID-7181 levels in the plasma, bile, urine, feces, and tissue homogenates and validated in a pharmacokinetic study. The plasma concentration of ID-7181 decreased to below the quantifiable limit at 6 h after the i.v. administration to rats following doses of 2-10 mg/kg, yielding a t(1/2,beta) of 77.7-81.7 t(1/2) after i.m. doses of 10-50 mg/kg were 79.3-127 min. The total plasma clearance (CLt) decreased with the nonlinear pharmacokinetics with an increase in the i.m. dose from 10 to 50 mg/kg in rats, while it was not significantly altered after the i.v. dose. The bioavailability of the i.m. administered ID-7181 was 43-63 %. Of the various tissues tested, ID-7181 was mainly distributed in the kidney after the i.v. or i.m. administration. The ID-7181 concentrations in the kidney 0.5 h after being administered i.v. or i.m. were comparable to the plasma concentrations shortly after being administered i.v. or the Cmax after being administered i.m. However, the ID-7181 concentrations in the tissues 6 h after being administered i.v. or i.m. decreased to low i.m. were 35-45 % of the initial doses. The corresponding values in the bile 6 h after being administered i.v. or i.m. were 0.5-1% of the initial dose. In conclusion, ID-7181, administered i.v. or i.m., is mainly distributed to the kidney. By 6 h after i.v. or i.m. administration, the ID-7181 concentrations in the various tissues decreased to very low levels. Moreover, the majority of ID-7181 appeared to be excreted in the urine.

Algorithms↗
PubMed1998

Direct intramuscular injection with recombinant AAV vectors results in sustained expression in a dog model of hemophilia.

A recombinant adeno-associated virus (rAAV) vector carrying the human factor IX cDNA was tested for safety and therapeutic gene expression in a canine model of human hemophilia B. Intramuscular delivery of rAAV was chosen based on our previous work which described long-term (> 1.5 years) reporter gene expression in immunocompetent mice following direct muscle injection. For the current study, rAAV with the human factor IX (hF.IX) cDNA under the control of the cytomegalovirus (CMV) immediate-early promoter was constructed, and rAAV/hF.IX proved capable of transducing hemophilic dog primary fibroblast cultures in a dose-dependent fashion. Direct intramuscular injection of 2.5 x 10(12) rAAV/hF.IX virus particles into the hindlimbs of a hemophilia B dog was tolerated without bleeding or systemic reaction, and the animal was asymptomatic throughout the entire study. Transient reduction in the whole blood clotting time (WBCT) occurred during the first week, with the anticipated development of an antihuman F.IX inhibitor antibody which corresponded with the loss of coagulation correction. At 10 weeks after vector administration, immunohistochemical analysis of injected muscle confirmed continued hF.IX expression. Limited areas of focal lymphocytic infiltration and myofiber pathology were detected which directly correlated with positive antibody staining for helper adenovirus contamination. PCR tissue analysis revealed rAAV/hF.IX DNA solely in injected muscle tissue and adjacent lymph node, without dissemination to other organs (including gonads). This first large animal study suggests that intramuscular gene delivery using rAAV vectors is safe and supports continued development of this approach for gene therapy of human diseases, including hemophilia B.

Animals↗
PubMed1996

Comparison of tenoxicam by intramuscular injection or wound infiltration for analgesia after inguinal herniorrhaphy.

We compared wound infiltration with small-dose tenoxicam (7.5 mg) to intramuscular (IM) administration of the same dose to treat pain after herniorrhaphy. In a randomized, double-blind study, 50 patients received either preoperative wound infiltration with tenoxicam, 7.5 mg in 40 mL of 0.9% saline (WI group; n = 25) or IM tenoxicam 7.5 mg (IM group; n = 25). In each group a saline placebo of equal volume was given by the alternate route, i.e., those who received wound infiltration with tenoxicam received 0.75 mL of 0.9% saline IM; those who received IM tenoxicam received 40 mL of 0.9% saline for wound infiltration. Postoperative pain was assessed with a verbal pain scale and a visual analog scale (VAS) at rest and during movement and cough, 1, 2, 4, 6, and 24 h postoperatively. Wound tenderness was assessed with an electronic algometer preoperatively, and 2, 4, and 6 h postoperatively. The need for supplementary analgesics (acetaminophen and morphine) was registered. No differences were observed between groups in VAS pain scores, verbal rating pain scores, pain pressure thresholds, or in need for supplementary analgesics. We conclude that tenoxicam 7.5 mg has no local analgesic effect on postoperative pain after herniorrhaphy.

Abdomen↗
PubMed1984

Clinical evaluation of intramuscular injection of microencapsulated compound megestrol acetate.

A comparative clinical study was undertaken by the Sichuan Cooperative Research Group for Microencapsulated Contraceptives to assess the efficacy of intramuscular microencapsulated megestrol compound as a long-acting contraceptive and to find the optimal dosage as regards efficacy, side effects and menstrual irregularities. Eight hundred twenty eight women were divided into four groups and injected monthly with four different dosage combinations that consisted of megestrol acetate and estradiol valerate. In all, 5298 dosage cycles were observed. The investigation indicated that microencapsulation effectively prolonged contraceptive effect of the short-acting agents, reduced the required dosage and lowered the incidence of side effects. A combination of 15 mg megestrol acetate and 5 mg estradiol valerate, as compared to the other three regimens, was found to be clinically most acceptable because of the lower incidence of menstrual irregularities.

Adult↗
PubMed2004

Diamorphine for pain relief in labour : a randomised controlled trial comparing intramuscular injection and patient-controlled analgesia.

OBJECTIVES: To compare the efficacy of diamorphine administered by a patient-controlled pump (patient-controlled analgesia) with intramuscular administration for pain relief in labour. DESIGN: Randomised controlled trial. SETTING: The South Glasgow University Hospitals NHS Trust. SAMPLE: Primigravidae and multigravidae in labour at term (37-42 weeks). METHODS: Women were randomised in labour to the study (patient-controlled analgesia) or control group (intramuscular). Randomisation was achieved through a random permuted block design stratified by parity. Study group women were given a loading dose of 1.2 mg diamorphine intravenously and then attached to the pump. Control group women received intramuscular diamorphine as per hospital protocol. Participants were also given 3 mg of buccal Stemetil. Data were collected throughout labour and at six postnatal weeks. MAIN OUTCOME MEASURES: Analgesia requirements during labour and women's satisfaction with the method of pain relief. RESULTS: Women in the study group (patient-controlled analgesia) used significantly less diamorphine than women in the control group (intramuscular) but were significantly more likely to state that they were very dissatisfied with their use of diamorphine and were significantly more likely to opt out of the trial before the birth of the baby. The majority of women in both groups used other analgesia concurrent with diamorphine such as Entonox, aromatherapy or TENS. CONCLUSIONS: Patient-controlled analgesia administration of diamorphine for the relief of pain in labour offers no significant advantages over intramuscular administration. The results also suggest that diamorphine is a poor analgesic for labour pain irrespective of the mode of administration.

Analgesia, Patient-Controlled↗
PubMed1997

Efficacy of replication-defective adenovirus-vectored vaccines: protection following intramuscular injection is linked to promoter efficiency in muscle representative cells.

To investigate the respective role of transduced cells in the induction of immune response following intramuscular inoculation of adenovirus-based vaccines, we generated several replication-defective adenoviruses expressing the glycoprotein D gene of pseudorabies virus under the control of four different promoters: major late promoter of adenovirus type 2, human cytomegalovirus immediate-early promoter/enhancer (CMV), Rous sarcoma virus-long terminal repeat promoter, and human desmin gene 5' regulatory region (DES). All the adenovirus constructs were able to fully protect mice, in the contrary of direct DNA inoculation of plasmids harboring the same transcription units. The far most effective adenovirus constructs, on the criterion of protective doses and specific antibody response induction, were those in which the foreign gene was driven by the DES or CMV promoter. Wide variations in promoter strength in vitro were evidenced in several cell culture types representative of putative target cells following muscular inoculation (myoblasts, myotubes, fibroblasts, macrophages, and endothelial cells). The level of efficacy in vivo, was not correlated with the level of expression in vitro in myotubes, but paralleled the level of expression in endothelial cells and in myoblasts. Together with previously published data, these results suggest that, following adenovirus injection, locally produced cytokines may induce myoblasts to act as local antigen presenting cells.

Adenoviruses, Human↗
PubMed2003

Effects on muscle pain by intramuscular injection of granisetron in patients with fibromyalgia.

We have previously reported that the level of 5-HT in the masseter muscle is increased in patients with fibromyalgia as compared with healthy subjects and that high intramuscular level of 5-HT is associated with muscle pain. We have also reported that injection of the 5-HT(3) receptor antagonist granisetron (GRA) into the masseter muscle of healthy subjects reduced pain induced by 5-HT and abolished allodynia/hyperalgesia. The aim of this study was to investigate whether GRA can influence pain and allodynia/hyperalgesia of the masseter muscle in patients with fibromyalgia. Eighteen female patients who met the criteria of fibromyalgia according to the American College of Rheumatology participated in the study. They were examined regarding pain intensity and pressure pain threshold (PPT) over the masseter muscle. One milliliter of GRA (1 mg/ml) was injected into the masseter muscle on one side and 1 ml of isotonic saline on the other side in a randomized and double-blind manner. After the injections, the pain intensity and PPT were recorded during 30 min. The pain intensity increased after injection of saline and to a lower degree after injection of GRA. The PPT increased after injection of GRA, while no such change was observed after saline. The difference between GRA and saline was, however, not significant. Eight of the patients responded to the GRA injection by an increase of PPT during the experimental period that differed from saline. They also showed a tendency to a lower increase of pain intensity after injection of GRA when compared to saline. In conclusion, the results of this study do not prove that injection of the 5-HT(3)-antagonist GRA into the masseter muscle influences local pain and allodynia/hyperalgesia in patients with fibromyalgia.

Adult↗
PubMedDate not supplied

Side effects of synthetic salmon calcitonin given by intranasal spray compared with intramuscular injection.

Side effects are the most frequent reason for discontinuing treatment with Calcitonin. Having been assessed in a previous report that the intranasal administration of Synthetic Salmon Calcitonin (SSCT) is as effective as its intramuscular administration, the aim of this work was to investigate the side-effects of intranasal administration of SSCT in patients who are known to show intolerance after intramuscular administration of the drug. The results show that intranasal administration of SSCT does not give rise to side-effects even in patients known to be intolerant to SSCT by the intramuscular route.

Administration, Intranasal↗
PubMed1978

A comparison of tissue gold levels in guinea-pigs after treatment with myocrisin injected intramuscularly and triethylphosphine gold chloride and myocrisin administered orally.

A comparative study of tissue gold levels produced in guinea-pigs after the oral administration of either triethylphosphine gold chloride or Myocrisin (sodium aurothiomalate) or after the injection of Myocrisin intramuscularly is reported. Gold concentrations were determined 5, 24 and 168 hours after administration in stomach, small intestine, large intestine, kidney, liver and spleen and 5 and 24 hours after administration in skin, adrenals, heart, lung and brain. In gastrointestinal tissues, tissue gold concentrations were highest with triethylphosphine gold chloride. The stomach gold level 5 hours after oral administration of triethylphosphine gold chloride is particularly high and, taken in conjunction with the other gastrointestinal gold levels measured, suggests that a stomach rather than an intestinal absorption mechanism may predominate. A more extensive time-course study on kidney and liver is reported and the possible relationship between tissue concentration and toxicity is discussed.

Administration, Oral↗
PubMed2004

Better efficacy of methotrexate given by intramuscular injection than orally in patients with rheumatoid arthritis.

OBJECTIVE: To compare the clinical efficacy of methotrexate and tolerance to the drug in patients with rheumatoid arthritis who were switched from intramuscular to oral administration because of a shortage of the intramuscular preparation. METHODS: 143 patients were switched from intramuscular to oral methotrexate. Of these, 47 were switched back to the intramuscular form. A multiple choice questionnaire was sent by mail to evaluate clinical and biological criteria of efficacy and tolerance. RESULTS: When methotrexate was first switched from intramuscular to oral administration, increased disease activity, exacerbation of morning pain and hand stiffness, duration of morning stiffness, increased joint pain, and increased joint swelling were observed. There was a greater frequency of gastrointestinal symptoms, but without a significant increase in liver abnormalities. When intramuscular methotrexate became available again, 47 of the 143 patients were switched back and were followed for at least three months. On average, disease manifestations were improved and side effects reduced by the switch. CONCLUSIONS: Methotrexate given intramuscularly had improved clinical efficacy with fewer side effects than given orally. Intramuscular methotrexate administration should be considered when rheumatoid arthritis remains active in spite of high dose oral methotrexate.

Administration, Oral↗
PubMed1976

Fluphenazine enanthate and fluphenazine decanoate: intramuscular injection and esterification as requirements for slow - release characteristics in dogs.

14C-Fluphenazine base was administered intramuscularly in sesame oil to five male beagles (2 mg/kg). The concentration of radioactivity in plasma and the excretion of radioactivity in urine and feces were measured for 14 days. Maximum concentrations of radioactivity were found in plasma 2 hr after administration. These levels declined with elimination half-lives of 3.20 hr during the 2-12-hr interval after dosing and of 4.02 days during the 2-14-day interval. Most administered radioactivity was excreted during the first 2 days after dosing, predominantly in the feces. An average of 0.43% of the dose was present at the injection site 14 days after dosing; some residual radioactivity was found in the liver and in the ocular portion consisting of the combined retina, choroid, and sclera. 14C-Fluphenazine and its enanthate and decanoate esters were each administered intravenously to three different groups of intact dogs at doses of 1 mg/kg. Regardless of which compound was administered, concentrations of radioactivity in the plasma of these dogs were comparable. Thirty minutes after these dogs had been dosed with 14C-fluphenazine enanthate or 14C-fluphenazine decanoate, most radioactivity in the plasma was present as 14C-fluphenazine base and other unidentified metabolites; at this time, at least 79% of either of the two 14C-fluphenazine esters had been biotransformed. The excretion of radioactivity by these same three groups of dogs was very similar, regardless of which of the compounds was given. In 7 days, an average of only 3-4% of the dose was excreted in urine; the remainder was excreted in feces. 14C Fluphenazine and its enanthate and decanoate esters (1 mg/kg) were administered intravenously to dogs whose bile ducts had been cannulated. The amounts of radioactivity excreted in the urine and bile in 8 hr were very similar, as were the residual amounts of radioactivity present in selected tissues. Comparison of the data obtained from dogs given these three compounds intravenously (unformulated) or intramuscularly in sesame oil points to the following conclusions: (a) fluphenazine base per se does not provide slow-release characteristics unless it has been esterified, for example, with heptanoic or decanoic acid, and (b) intramuscular rather than intravenous administration of these two esters is responsible for producing their slow-release characteristics.

Animals↗