Prolonged release from the injection site of morphine from morphine esters in an oil vehicle given by intramuscular injection to pigs.
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The effects of intramuscular (i.m.) injection of a sub-lethal dose of cobra venom (0.015 microgram/gm body weight) on the histological and histochemical patterns of the kidney of rabbit were examined after 3, 6, and 12 hr. of envenomation. The histological observations after 3 hr. of envenomation showed glomerular congestion together with slight swelling of the cortical tubular epithelia. However, no changes were recorded in the medullar tubules. Serious alterations were recorded after 6 hr. of envenomation. It included thickening of the Bowman's capsules, signs of mesangiolysis, and glomerular collapse. The cortical tubular epithelia were swollen and revealed cytoplasmic granulation, coagulation, or depletion. Nuclear pyknosis and cellular damage were recorded in some areas. The medullar tubules showed cytoplasmic degeneration with no nuclear changes. By 12 hr. of envenomation a higher degree of severity was recorded. The glomerular tufts were hypertrophied or suffered from partial damage. Mesangiolysis and glomerulolysis were common and some glomerular tufts were completely transformed to clumps of hyaline casts. The cortical tubules showed hyaline coagulation, together with severe tubular damage in which the boundaries of the individual tubule cannot be identified. Numerous inflammatory cells were observed invading the damaged epithelial cells and the intertubular spaces. The medullar tubules showed swollen epithelia with cytoplasmic changes and nuclear pyknosis or karyolysis. Histochemically, the polysaccharide inclusion was increased in the glomerular tufts, the Bowman's capsules, and the basement membranes and brush borders of the renal tubules after 3 and 6 hr. of envenomation. By 12 hr. of envenomation, decreased PAS reactivity was recorded in all renal components except the glomerular tufts which exhibited intensive reactivity. Time-dependent depletion of lipid, protein, and RNA components was recorded in the renal tissues of the three envenomed groups. However, no changes in DNA reactivity were detected in renal tissues of the 3 hr. envenomed group. The nuclei of certain renal tubules revealed weak DNA reactivity after 6 hr. of envenomation, while most of the nuclei lost their contents by 12 hr. of envenomation. The results indicated serious histological and histochemical alterations induced in the renal tissues by 6 hr. of envenomation. Such alterations could indicate a disturbance in the functional activity of the kidney during envenomation. Therefore, nephrotoxicity should be considered as one of the serious consequences of such venom.
A randomized investigation compared the efficacy and safety of nalbuphine administered by two methods, a patient-controlled infuser system and intramuscular (IM) injections, after major gynecologic surgery. Forty-seven patients were randomly assigned to receive nalbuphine by either method. The 22 patients using the infuser were given a 2.0-mg, incremental dose with a 10-minute lock-out interval between doses. A similar group receiving 10-15 mg IM every three hours served as the control. Misprogramming, overdosage, depressed respiration and drug dependence were not encountered. Self-administration provided equally satisfactory sedation and more immediate pain relief without painful injections. Although patients with the infuser had the ability to self-administer more medication, they did not use higher doses of nalbuphine than did the IM group. The additional cost of the infuser system was offset by the satisfaction expressed by the patients and by the improved nursing efficiency. Nalbuphine administered with a patient-controlled infuser provided an effective balance between analgesia and sedation and offered advantages over IM injections.
During March-april 1996, a physician in the Denver area administered intramuscular injections of a preparation labeled "adrenal cortex injection" to 69 patients in Colorado as part of a weight-loss regimen. As of August 7, a total of 47 (68%) of these persons were reported to have developed abscesses (diameters ranging from 0.5 cm to 4.0 cm) at the site of injection (either gluteal or deltoid muscle). An investigation of these episodes by the physician and the Colorado Department of Public Health and Environment identified Mycobacterium abscessus as the cause of the infections. This report summarizes preliminary findings of the ongoing investigation, which indicate that injection-site abscesses were associated with contaminated injectable preparations.
OBJECTIVE: The pharmacokinetics and efficiency of human chorionic gonadotropin (hCG) after subcutaneous (SC) injection was to clarify in comparison with the intramuscular (IM) mode of administration. DESIGN: In a prospective study, the pharmacokinetics of hCG and the response of serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) after an IM and SC injection of 5,000 IU hCG were evaluated up to 144 hours in two randomized groups. SETTING: The study was carried out in a clinical dermatology department providing tertiary care. PARTICIPANTS: Twenty-four healthy male volunteers with a mean age of 22.7 +/- 4.3 years were divided into two groups. INTERVENTIONS: Human chorionic gonadotropin (5,000 IU) was injected IM or SC. MAIN OUTCOME MEASURE: Serum concentration of /b-hCG, T, LH, and FSH were evaluated after IM and SC administration of hCG. Differences between the two groups were determined by t-test. RESULTS: Compared with IM administration of hCG, peak serum drug concentration was significantly delayed (P = 0.01) and serum half-life was prolonged (P = 0.01) after SC injection; however, T, LH, and FSH responses were identical. CONCLUSIONS: Subcutaneous application of 5,000 IU hCG is as effective as IM administration in terms of steroidogenesis.
OBJECTIVE: To investigate the suitability of intramuscular testosterone undecanoate (TU) injections for substitution therapy in hypogonadal men. STUDY DESIGN: Clinical, open-label, non-randomized trial of 13 hypogonadal men receiving 4 intramuscular injections of 1000 mg TU in 4-ml castor oil at 6-week intervals. General wellbeing, sexual parameters, clinical chemistry, hormone levels, prostate size and prostate-specific antigen (PSA) were evaluated over 24 weeks and compared with baseline values. RESULTS: Testosterone serum levels were never found below the lower limit of normal and only briefly after the 3rd and 4th injection above the upper limit of normal, while peak and trough values increased over the 24-week observation period. Oestradiol and dihydrotestosterone followed this pattern, not exceeding the normal limits. No serious side-effects were noted. Slight increases in body weight, haemoglobin, haematocrit, prostate volume and PSA, suppression of gonadotrophins as well as increased ejaculation frequency occurred as signs of adequate testosterone substitution. CONCLUSION: Testosterone undecanoate is well tolerated by the patients. The injection intervals can be extended even beyond the 6-week periods chosen in the present study. Altogether, intramuscular testosterone undecanoate appears to be well suited for long-term substitution therapy in hypogonadism and hormonal male contraception.
Antiphlogistic and Analgetic Activity of Etofenamate in Laboratory Animals after Intramuscular Administration by injection of an oily solution of 10.5; 15; 19.5 mg etofenamate/kg body weight it was possible to inhibit the development of the carrageenan edema in the rat paw. Even four days after the single i.m. injection of etofenamate (active substance of Rheumon i.m.) the swelling of the rat paw is effectively prevented. By the Randall-Selitto-analgesia test it was possible to demonstrate the fast onset. Already 1 h after the injection of 15 mg/kg the pain threshold is increased to about 60%. Even in this testsystem the prolonged efficacy of oil diluted etofenamate can be found.
For studies of motor neuron function or for therapeutic purposes, novel pseudotype HIV-1-based vectors were developed that are capable of expressing transgenes in motor neurons following injection into mouse hind limb muscles. To specifically target motor neurons, glycoproteins from two rabies virus (RV) isolates, the mouse-brain adapted challenge virus 24 (CVS-24) variants, CVS-N2c and CVS-B2c were evaluated for pseudotype formation with an HIV-1-based vector. Both RV glycoproteins incorporated into vector envelopes, and both pseudotypes yielded high titers with Hek293T and cortical plate neuron cultures. Increased neuronotropism by the CVS-N2c pseudotype was not observed, suggesting that vector tropism is not solely determined by the fusogenic viral glycoprotein. Vector injection into hind limb muscles resulted in EYFP reporter gene expression in the injected muscle fibers and in spinal cord motor neurons innervating the same muscle, indicating retrograde vector transport. Intramuscular vector injections into the soleus and tibialis anterior muscles transduced 26% and 16% of all motor neurons in each motor nucleus, respectively. These transduction efficiencies may allow novel approaches to functional studies of the motor system and the treatment of neuromuscular disease.
The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the 133Xe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125I-insulin increased during exercise from 0.46 +/- 0.08 to 1.17 +/- 0.14%/min after intramuscular injection (P less than 0.001) and from 0.31 +/- 0.05 to 0.45 +/- 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was approximately 80% greater, and the decrease in plasma glucose was approximately 2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
A 25-year-old male patient presented with foot drop indicative of a sciatic nerve injury following gluteal intramuscular (IM) injections. Blood tests and magnetic resonance imaging of his spine were within normal limits, but electrophysiological studies confirmed a partial sciatic nerve lesion. The course of the sciatic nerve in the gluteal region places it at risk for injury from IM injections. Proper technique minimizes the risk of injury.
Ceftiofur sodium, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance. Two studies were designed to compare the intramuscular bioavailability of the current sodium salt and the new hydrochloride salt in pigs at doses of either 3 mg or 5 mg ceftiofur equivalents (CE)/kg body weight. Twenty-six healthy young pigs were selected for these two-period, two-treatment crossover studies, 12 for the 3 mg/kg study and 14 for the 5 mg/kg study. Each animal received one intramuscular (i.m.) injection of ceftiofur sodium and one i.m. injection of ceftiofur hydrochloride with a 14-day washout period between the two treatments. Blood samples were collected serially for up to 96 h postinjection. Plasma samples were then analysed using a validated assay that measures ceftiofur and all desfuroylceftiofur-related metabolites by high-performance liquid chromatography. In the 3 mg/kg dosage study, average maximum plasma concentration (C(max)) after administration of ceftiofur sodium was 15.8+/-3.40 microg/mL at 0.4-4 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 11.8+/-1.67 microg/mL at 1-4 h after injection. Concentrations of ceftiofur and metabolites 72 h after the injection were 0.392+/-0.162 microg/mL for ceftiofur hydrochloride and 0.270+/-0.118 microg/mL for ceftiofur sodium. The mean area under the curve (AUC), from time 0 to the limit of quantitation (AUC(O-LOQ)) after ceftiofur hydrochloride administration, was 216+/-28.0 microg x h/mL, compared to 169+/-45.4 microg x h/mL after ceftiofur sodium administration. The calculated time during which plasma concentrations remained above 0.02 microg/mL (t(>0.2)) was 85.3+/-10.6 h for ceftiofur sodium and 77.2+/-10.7 h for ceftiofur hydrochloride. In the 5 mg/kg dosage study, C(max) after administration of ceftiofur sodium was 28.3+/-4.45 microg/mL at 0.33-2 h after injection. After administration of ceftiofur hydrochloride, the C(max) was 29.7+/-6.72 microg/mL at 0.66-2 h after injection. Concentrations of ceftiofur and metabolites 96 h after the injection were 0.274+/-0.0550 microg/mL for ceftiofur hydrochloride and 0.224+/-0.0350 microg/mL for ceftiofur sodium. The mean AUC(O-LOQ) after ceftiofur hydrochloride administration was 382+/-89.8 microg x h/mL compared to 302+/-54.4 microg x h/mL after ceftiofur sodium administration. The t(>0.2) was 78.9+/-9.65 h for ceftiofur sodium and 94.2+/-8.64 h for ceftiofur hydrochloride. Based on the similarity of the pharmacokinetic parameters of the sodium and hydrochloride formulations of ceftiofur, similar therapeutic efficacy can be inferred for the two products.
A short-term toxicity study was performed to investigate local reactions and haematological changes after intramuscular (i.m.) injection of meningococcal vaccine with a concentration of 25 or 50 micrograms protein ml-1. In these meningococcal vaccines up to 75 micrograms Zwittergent ml-1 was used to form a protein-detergent complex with attractive immunogenic properties. The Zwittergent preparations were treated with NaOH in order to destroy any propane sultone residue and this was checked by HPLC. The effects were compared with those caused by a sterile phosphate-buffered saline solution and by diphtheria-pertussis-tetanus-polio (DPT-polio) vaccine. Groups of six male rats were injected i.m. with 0.25 ml of the test solution, on day 0 in the left, and on day 7 in the right, quadriceps muscle. On day 14 the animals were exsanguinated under ether anaesthesia and, after gross inspection, inguinal nodes were weighed. These lymph nodes and the left and right quadriceps muscles were studied microscopically. In addition, a haematological investigation was performed. A significant increase in the number of thrombocytes was seen in animals receiving the DPT-polio and meningococcal vaccines containing 25 micrograms protein ml-1, and an increase in the number of leucocytes, due to an increase of neutrophils and monocytes, was seen in animals receiving the DPT-polio and meningococcal vaccine containing 50 micrograms protein ml-1. In comparison with the DPT-polio vaccine (a product generally acceptable for use in man), the local inflammatory reaction in the muscles was less in rats injected with the meningococcal vaccines (especially in the 25 micrograms protein ml-1 group).(ABSTRACT TRUNCATED AT 250 WORDS)
Five Zebu x British crossbred bulls 17 months of age and of uniform liveweight (320+/-3 kg) were used to study testosterone responses to single intramuscular doses of exogenous gonadotropin-releasing hormone (GnRH). The eight dose levels used were 0, 31.25, 62.5, 125, 250, 500, 1000, and 2000 ng GnRH/kg live weight. Plasma samples for hormone responses were collected at 30-minute intervals from zero to three hours and at one-hour intervals from three to seven hours postinjection. Luteinizing hormone (LH) and testosterone responses were measured as peak heights or as areas under response curves. Increasing the dosage of GnRH increased the time to reach the peak LH response, the height and duration of the response, and the area under the response curve. The maximum LH peak height was reached by the 1 mug/kg dose. In contrast to LH, testosterone responses reached the same peak heights (two hours postinjection of GnRH) for all doses of GnRH. The only effect of increased dosage was to increase the duration of response. Testosterone responses showed repeatable differences (P<0.01) between animals, but LH responses did not. It was demonstrated that the testosterone status of bulls can be accurately assessed by simply measuring testosterone in a single plasma sample collected two to three hours after the intramuscular injection of 100 mug or more (dose unimportant) of GnRH per bull.
We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased. Each of four genetically engineered variants (one variant with growth factor and kringle 1 domains deleted and kringle 2 duplicated, a second variant with a cysteine for Arg substitution in the growth factor domain, a third variant with an additional urokinase kringle inserted, and a fourth variant with the growth factor domain deleted) and enzymatically deglycosylated t-PA exhibited prolonged half-life after bolus intravenous injection in rabbits. Each elicited substantially higher and more sustained elevations in plasma after intramuscular injection in rabbits or dogs with absorption-enhancing agents as compared with wild-type t-PA that were not accompanied by a systemic lytic state. Thus, use of molecular variants of t-PA with prolonged half-lives in the circulation permits induction of augmented and sustained elevations of plasma concentrations after intramuscular injection with absorption-enhancing agents as compared with wild-type t-PA, rendering potentially therapeutic blood levels more attainable with relatively modest amounts of material.
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AIM: The aim of the study was to compare the pharmacokinetics and glucodynamics of insulin lispro and soluble human insulin following intramuscular (i.m.) injection in patients with Type 2 diabetes with secondary failure of sulphonylureas. METHODS: Single 15-U i.m. doses of insulin lispro or soluble human insulin were administered to 16 patients in a two-way, randomized, crossover design. Glucodynamic and pharmacokinetic parameters were determined over 6 h after insulin injection using clamp techniques. RESULTS: Insulin C(max) was significantly higher (971 +/- 217 vs. 659 +/- 141 pmol/l, P < 0.001) and T(max) was significantly shorter (46.9 +/- 27 vs. 94.7 +/- 50.1 min, P = 0.002) with insulin lispro. Glucose infusion rate (GIR) curves showed clear separation 20 min after injection and were significantly greater for insulin lispro during the 40-60, 60-80 and 80-100-minute time intervals. Total glucose infused was only approximately 5% larger with insulin lispro during the 6-h follow-up, due to lower insulinaemia at later time points. The glucose R(max) and TR(max) were not statistically different between insulin treatments. CONCLUSION: This study shows that i.m. injection of insulin lispro is followed by its more rapid absorption, which results in stronger metabolic effect in the first 2 h when compared with soluble human insulin under the same test conditions. Diabet. Med. 18, 562-566 (2001)
At 11 to 13 d after insemination, 1028 dairy cows on 19 farms were given an intramuscular injection of 10 micrograms of the GnRH analogue buserelin. Their reproductive performance was compared to 1022 control cows receiving a placebo. The GnRH analogue-treated cows had fewer short interoestrous intervals compared to the control cows, but there were no significant differences in pregnancy rates to either the insemination preceding or following treatment, in calving to conception interval, or to percent pregnant by the end of mating. There were no differences between treatments in herds of high, average or low pregnancy rate, in 2-year-old cows or cows greater than 2-years-old and in cows calved 40 d or less, or greater than 40 d. The use of 10 micrograms of the GnRH analogue, buserelin, 11 to 13 d after insemination, cannot be recommended as a method of improving reproductive performance in dairy herds.
Clonidine (Catapres) administered intramuscularly in a dose of 150 microng produced a satisfactory reduction in blood pressure in 13 of 16 hypertensive patients. Its effect occurred within five minutes, was maximal at 75 minutes and persisted for five hours. In six patients who received two doses (150 microng and 300 microng), the response was shown to be dose-related. No serious side effects were noted. Intramuscular administration of clonidine thus appears to be safe and effective. It has a place in the management of uncontrolled hypertension when a rapid reduction in blood pressure is undesirable and in the maintenance of blood pressure control when oral therapy cannot be tolerated.