Intramuscular Route Of Administration Research Articles

Clinical and endocrine response to pulsatile intravenous gonadotropins in refractory anovulation

We investigated the endocrine response to an experimental protocol in which human menopausal gonadotropin was delivered in pulses every 90-120 minutes by an automated pump. Thirty clomiphene citrate- and gonadotropin-releasing hormone-unresponsive anovulatory women were studied over 107 treatment cycles. In response to episodic intravenous (IV) delivery, pulses of FSH and LH were demonstrable in the circulation. In four World Health Organization (WHO) group I anovulatory women, ovulation occurred in all cycles (N = 8); the pregnancy rate per cycle was 63% and the cumulative pregnancy rate 100%. In 26 WHO group II patients, 42.4% of treatment cycles were in 12 women previously refractory to the intramuscular route of administration; the rate for ovulation was 86% (total of 99 cycles), the pregnancy rate per ovulatory cycle was 14%, and the cumulative pregnancy rate 56%. A mild phlebitis occurred at the site of the IV catheter in 24% of treatment cycles. Intravenous delivery of gonadotropins in small pulses had a dose-sparing effect and was an effective method of treating anovulatory infertile patients refractory to other conventional methods of ovulation induction.

Recombinant interferon-gamma lacks activity against metastatic colorectal cancer but increases serum levels of CA 19-9.

A clinical trial to determine the antitumor activity of recombinant interferon-gamma (rIFN-gamma) was conducted in 36 patients with advanced colorectal cancer. Severe constitutional symptoms were seen in the first five patients who received rIFN-gamma as a 2- to 4-hour intravenous infusion, and this method of administration was therefore abandoned. One transient partial tumor regression was observed in the 31 patients who received treatment by the intramuscular route of administration. Although a clinically tolerable regimen suitable for outpatient administration was developed, rIFN-gamma given in this dose and schedule had minimal antitumor effect for the treatment of advanced colorectal cancer. NK activity was depressed within 48 hours of rIFN-gamma administration but became significantly higher than normal controls or pretreatment levels during therapy despite disease progression, indicating discordance between augmentation of this immune parameter and tumor status. Serum CA 19-9 levels were unusually high and increased significantly more than CA 125 or CEA during rIFN-gamma treatment. This observation suggests that rIFN-gamma could augment localization of anti-CA 19-9 used to diagnostically image or therapeutically target a labeled chemotherapy agent to tumor in those patients expressing this antigen.

Rabies Pre-Exposure Prophylaxis Using Intradermal Human Diploid Cell Vaccine: Immunologic Efficacy and Cost-Effectiveness in a University Medical Center and a Review of Selected Literature

The authors studied the antigenicity of intradermal human diploid cell rabies vaccine administered to 40 laboratory workers considered to be at-risk at the University of Virginia Medical Center. A 1-year postvaccination serology was determined for 20 of those 40, all of whom demonstrated an antirabies titer greater than or equal to 1:50 by the raped fluorescent focus inhibition test. By 2 years' postvaccination, 5 of 40 subjects had "unprotective levels" (less than 1:5), whereas 35 had titers greater than or equal to 1:5, and none had a titer greater than or equal to 1:50. Booster doses given to four subjects whose titers had declined produced a 1-month postvaccination antirabies titer greater than or equal to 1:50 in all cases. Vaccine administration by the intradermal rather than the intramuscular route resulted in a cost savings of $120 (U.S.) per employee. This data indicate that the intradermal administration of human diploid cell vaccine for rabies pre-exposure prophylaxis achieves an immunologic response thought to be protective while providing a substantial cost savings when compared with the intramuscular route of administration. Those who receive primary pre-exposure rabies vaccination should have serologic confirmation of immunologic protection every 2 years with a booster dose given to subjects demonstrating a titer less than 1:5.

Des-enkephalin-γ-endorphin: bioavailability in rats following the subcutaneous and intramuscular route of administration

A pharmacokinetic study with [ 3H]des-enkephalin-γ-endorphin ( 3H-DEγE) was performed in rats after the intraveous, subcutaneous and intramuscular route of administration. Disappearance of non-metabolized 3H-DEγE from blood upon intravenous dosing followed a biphasic decay with half-lives of 0.7 ± 0.3 (± S.D.) min for the initial distribution phase and 6.3 ± 2.7 min for the terminal elimination phase. The central and peripheral volumes of distribution were strikingly high (0.38 and 0.55 1 · kg −1, respectively). Extensive metabolism occurred already within the first minutes after injection. The blood clearance rate was found to be 0.29 ± 0.12 1 · min −1 · kg −1 , which value points to remarkable extrahepatic elimination of the neuropeptide. As compared to the intravenous route of administration, subcutaneous or intramuscular injection of 3H-DEγE resulted in low but longer-lasting peptide levels in blood. These levels reached already peak values at 2 min after both routes of administration and then declined to below the limit of detection at 2–3 h. The absolute bioavailability of DEγE after subcutaneous injection amounted to 30.9 ± 16.3% (range 16.0–46.9%), whereas the bioavailability after intramuscular injection was observed to be 3.5 times lower ( 8.5 ± 3.0%; range 4.6–12.0%). These data suggest that subcutaneous dosing of DEγE might be more effective in displaying CNS activity than the intramuscular route.

The pharmacokinetics of HI-6 in beagle dogs.

The pharmacokinetics of HI-6 were studied following intravenous administration to beagle dogs (n = 7). The bioavailability of two different strength intramuscularly administered doses was also determined in the same animals. After a 20 mg kg-1 intravenous dose, the mean (+/- S.D.) initial HI-6 plasma concentration was 93.1 +/- 10.8 micrograms ml-1. The mean half-life was 48.2 +/- 17.7 min, the mean total body clearance was 5.16 +/- 0.81 ml min-1 kg-1, the mean apparent volume of distribution was 0.37 +/- 0.20 l kg-1 and 61.2 +/- 14.6 per cent of the dose was excreted as unchanged drug. The pharmacokinetic constants calculated following the 20 mg kg-1 intramuscular doses of 250 and 25 mg ml-1 solutions were not significantly different from those obtained following the intravenous dose. Also, the areas under the plasma concentration versus time curves were not significantly different indicating 100 per cent bioavailability from the intramuscular route of administration.

Clinical evaluation of prophylactic regimens for bovine respiratory disease

Experiments were conducted using a 3 by 2 factorial design to evaluate the efficacy of Haemophilus somnus and unspecified Pasteurella inactivated vaccines and to compare the oral and intramuscular route of administration of a BVD vaccine. 303 crossbred steer calves with an average weight of 222 kg were purchased and any animal showing clinical signs of illness excluded. All calves in the trial received an intranasal IBR vaccine, 2.5 million units of vitamin A intramuscularly, three 36 mg implants of zeranol, multivalent clostridial vaccine and levamisole. Calves were randomly assigned to treatment groups by a random number table. 45 randomly-selected calves distributed among all treatment groups were bled during processing and again 42 days after vaccination to collect paired samples. The calves were checked daily and any with clinical signs of respiratory disease were treated. The calves were weighed on arrival and at 34, 72 and 106 days, and daily feed consumption was calculated. The pasteurella vaccine reduced the incidence of BRD and improved the response to treatment. The result disagrees with previous findings, perhaps because of differences in prior exposure, movements in marketing channels or the virulence of the bacteria. The BRD morbidity rate and response to treatment were no different for the oral and intramuscular route of administration. However, the immune response to the BVD vaccine as measured by serum neutralisation was greater following oral administration.

Release of contraceptive progestogens from biodegradable systems

Hormonal contraceptives remain the most widely utilized form of female fertility regulation. Progress in the field has been achieved through the search for a lower dose regimen to avoid adverse reactions such as thromboembolic complications. Introduction of hormonal contraceptives into the developing world has led to the development of preparations of long acting formulations or the synthesis of long acting derivatives of steroids that could be injected and would provide protection against pregnancy without added estrogen. 2 drugs are utilized: medroxyprogesterone acetate in a depot mycrocrystalline formulation and a heptanoic acid ester of norethisterone. Unfortunately longterm injectable progestogens expose the body to unnecessarily high plasma concentrations not required for the contraceptive effect. Sustained release derivatives producing release profiles close to zero order can be prepared however a certain degree of cycle disturbance is unavoidable. Polymeric drug delivery systems have been developed which include capsules rods and pellets placed under the skin; microcapsules for intramuscular injection; and various devices for delivery to the vagina uterus and fallopian tubes. Biodegradable polymers have been investigated for infusion controlled devices the most successful have been the polyesters. Attempts have also been made to use the rate of erosion of the polymer in the body as the controlling mechanism. Both systems however are dependent on the specific drug used. The use of polymers for the intramuscular route of administration primarily has been with microspheres. Poly(lactic acid) has been the polymer of choice. Reasonable approximations of zero order release have been obtained with microcapsules containing norethisterone. The use of polypeptides is another approach to sustained drug delivery which could be used intramuscularly. Polysiloxane rings releasing steroids for delivery through the vagina have been prepared. Devices have been tested using synthetic progestogen with naturally occurring estrogen and progestogen only. The rationale for using low doses of progestogen is to maintain a more normal endocrine profile and menses through interference with the reproductive processes at a level peripheral to the ovary as opposed to inhibiting ovulation. Local delivery at the site of action is also possible and has been achieved with devices such as IUDs which release progestogens. Sustained release systems can usefully be applied to the delivery of androgen-progestogen combinations. Testicular steroid production is more uniform with time making a zero order system an ideal tool for the delivery of contraceptive steroid combinations.

Abortion with sulprostone, a prostaglandin E2 derivative.

Sulprostone, a prostaglandin E2 derivative, was used in a multicenter trial to terminate 478 pregnancies of 8-21 weeks' gestation. The compound was clinically well accepted without premedication in extraovular, intravenous and intramuscular routes of administration. At 24 hours after treatment, 67%-88% of the patients had aborted, with a low average incidence of side effects. Sulprostone is preferred clinically to primary prostaglandins. Intravenous infusion was found to be the safest route, but intramuscular injection proved to be the most practical.

Cefoxitin in Treatment of Obstetric and Gynecologic Infections

Cefoxitin was found to be an effective and safe agent for the treatment of infections of the female genital tract that were associated with a variety of aerobic and anaerobic bacteria, including Streptococcus, Escherichia coli, and Bacteroides species. The overall clinical response was 91%. The major cause of failure was the presence of an abscess requiring surgical drainage. Both the intravenous and the intramuscular routes of administration for cefoxitin were tolerated well or moderately well by most patients.

Systemic Toxic Reactions to Procaine Penicillin G

Systemic toxic were encountered in eight of 10,469 patients during or immediately following the intramuscular injection of 4,800,000 units of procaine penicillin G for the treatment of gonorrhea. Fear of imminent death, visual and auditory disturbances, violent combativeness, confusion, disorientation, and restlessness, disturbance in taste, cardiovascular changes, and grand mal seizures are the principal manifestations; these usually subside in two to 10 minutes spontaneously or after treatment. Symptoms and signs closely parallel systemic toxic reactions to local anesthetics. Pharmacokinetic analysis in dogs using 14C-procaine and 14C-procaine penicillin G showed rapid distribution of labeled drugs from plasma to cerebrospinal fluid for the intravenous as compared to the intramuscular route of administration. The animal studies were consistent with the hypothesis that the inadvertent intravenous administration of procaine penicillin G is responsible for the systemic toxic reactions. Plasma procainesterase (pseudocholinesterase) activity was assayed with an ultraviolet spectroscopic method. Substrates were procaine and procaine penicillin G. The plasma procainesterase activity of patients who had experienced systemic toxic reactions was significantly decreased as compared to that of controls, an observation not previously reported.

The Clinical Pharmacology of Methylprednisolone Sodium Phosphate. I. Intramuscular Route of Administration

Intramuscularly administered methylprednisolone sodium phosphate (Medrol Stabisol) in single doses of 40, 80, or 160 mg (methylprednisolone equivalents) had a similar effect as the same doses of methylprednisolone sodium succinate (Solu-Medrol) with regard to eosinophil suppression, elevation of glucose, white blood count differential shifts (lympholytic effect), urinary excretion of sodium and potassium, and localized (pain) and systemic side effects. The average plasma methylprednisolone concentration was approximately 20% higher after the intramuscular administration of methylprednisolone sodium phosphate than after methylprednisolone sodium succinate. The differences in plasma methylprednisolone levels produced by the two esters suggest that either hydrolysis of the succinate ester occurs more slowly or the succinate ester distributes more extensively. This difference in plasma level, however, is not reflected in any other pharmacologic evaluation of the two esters, e.g., both eosinophil depression and hyperglycemic response were identical. No clinically significant changes in the vital signs, standard hematology, and clinical chemistry parameters evaluated were noted after 21 successive doses (q.i.d. for five days with one dose in the morning of day 6) of 80 mg methylprednisolone sodium phosphate. An increase was noted in the systolic blood pressure from a pretreatment mean of 113 mm Hg to a posttreatment mean of 123 mm Hg and an increase in the body weight from a pretreatment mean of 177 pounds to a posttreatment mean of 183 pounds. No signs of adrenal suppression were found as judged by plasma cortisol and ACTH levels. Six (6/12) subjects of the methylprednisolone sodium phosphate group, one (1/12) subject of the vehicle group, and one (1/12) subject of the placebo (sterile saline) group reported the following systemic side effects: gas in stomach, headaches, anorectal itching, and dryness of itching of the skin. No trend was observed for any side effect reported. In these double-blind, randomized studies, single (40, 80, and 160 mg) and multiple (80 mg) intramuscular doses of methylprednisolone sodium phosphate were tolerated in healthy volunteers as well as the same doses of methylprednisolone sodium succinate and similar volumes of vehicle or placebo.

The clinical pharmacology of meperidine--comparison of routes of administration.

The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered.

Midtrimester abortion with intramuscular injection of 15-methyl-prostaglandin E 2

An intramuscular injection of 10 ug of 15-methyl-PGE 2 was given to twenty patients every two hours until the fetus was expelled or for a maximum of eight injections. Within 24 hours, 95% aborted with a mean injection-abortion time of 9.1 hours. Seventy-five percent aborted completely, 20% aborted incompletely, and 5% (1 patient) failed to abort. In an attempt to reduce vomiting, 15 patients received chlorpromazine 25 mg one-half hour prior to administration of the prostaglandin. Ten patients experienced one or more episodes of vomiting, four out of five without chlorpromazine and six out of fifteen with chlorpromazine. Seventeen experienced one or more episodes of diarrhea. Additionally, all 20 experienced “shivering” and had a temperature elevation of at least 1.8 °F which returned to normal shortly after abortion. No serious complications occurred. The results of this study suggest that 15-methyl-prostaglandin E 2 is effective for midtrimester abortion when given by the intramuscular route of administration.

Distribution of parenteral ampicillin and cephalosporins in late pregnancy.

SummaryWhen ampicillin is given by intramuscular injections at six‐hourly intervals to pregnant women, it reaches levels in the fetus which are almost one‐third of the maternal levels. The delay in reaching the liquor amnii is less than after oral administration of antibiotic and after four to six hours reaches 4 μg. per ml. There is no evidence of accumulation with repeated dosage. Cephaloridine behaves in a similar manner to ampicillin and there is no evidence of accumulation in the fetus. Cephalothin produced short‐lived high levels in the maternal serum but in the liquor amnii levels of 4 μg. per ml. were reached very rapidly and sustained. Only small quantities of cephalothin were found in the fetus and it is considered that this was related to the route of administration. The findings suggest that when ampicillin, cephaloridine or cephalothin are used to treat severe intrauterine infections during labour, both the intravenous and intramuscular routes of administration should be used as the former quickly give high levels of antibiotic in liquor amnii, while the latter give sustained levels in the fetus.

Control of convulsions by intralingual administration of barbiturates

This article demonstrates the efficacy of the intralingual route of injection of pentobarbital for emergency use in the convulsing patient in the dental office. The intralingual route is compared directly against the intravenous and intramuscular routes of administration, and the advantages of the intralingual route are discussed. In the average dental office, where personnel are relatively untrained in the emergency intravenous administration of drugs, the intralingual route might well be the best choice for use in this situation.

Reevaluation of Ampicillin Therapy for Hemophilus influenzae Meningitis

Three cases of persistence or relapse of infection inHemophilus influenzaetype b meningitis treated with ampicillin sodium are presented. Factors that may have contributed to bacteriological failure were infection of the subdural space, the use of the intramuscular route of administration, the presence of ventriculitis and hydrocephalus, and the development of a brain abscess due toH influenzae.Eight previously reported cases of ampicillin failure were also reviewed to determine possible reasons for failure. These included inadequate dosage, intramuscular administration, and sequestration of organisms in inaccessible sites. On the basis of available information it is recommended that ampicillin should remain the drug of choice for the treatment ofH influenzaemeningitis since there is little reason to believe that reinstating chloramphenicol as the preferred drug would produce better results.

Evaluation of a synthetic 25 amino acid corticotrophin in normal man.

A synthetic 25 amino acid corticotrophin was evaluated in normal man. Graded doses of the corticotrophin (DW‐75) were administered intramuscularly to 4 subjects and intravenously to 4 subjects. Urinary 17‐ketosteroids and 17‐hydroxycorticosteroids and plasma cortisol responses were measured. The intramuscular route of administration resulted in little change from the control periods in the parameters monitored. The drug had a potent adrenocortical‐stimulating effect when administered intravenously. No side effects were encountered during the study.

Comparison of intramuscular and oral ampicillin therapy for shigellosis

Twenty-four patients with severe shigellosis were treated with intramuscular ampicillin, 100 mg. per kilogram per day in 4 divided doses for 5 days. They were compared with patients previously treated orally with the same dosage of ampicillin. Clearing of Shigellae from the stools was significantly more rapid with the intramuscular route of administration. Alterations in enteric flora were different in the 2 groups. Patients treated orally were more likely to have the intestinal flora replaced with Candida species in contrast with those treated parenterally who were more apt to have overgrowth with species of Klebsiella-Aerobacter. Though each mode of ampicillin administration is effective in the treatment of shigellosis, the intramuscular route results in a more prompt eradication of Shigellae and is useful in the treatment of patients who are not able to take medication orally.

Intravenous diphenylhydantoin in experimental seizures. I. Correlation of dose, blood, and tissue level in cats.

DIPHENYLHYDANTOIN, used orally, is one of the most effective drugs available for the prevention of seizures. The oral or intramuscular routes of administration require the passage of hours to days, however, to achieve therapeutic blood levels, even when large loading doses are used. 1-5 For these reasons, the availability of an intravenous preparation of diphenylhydantoin for status epilepticus, was welcomed. Recent studies from our laboratories, showed that as much as 1,000 mg could be given safely to patients by the intravenous route, provided certain precautions were observed. 6 Well-sustained blood levels of diphenylhydantoin were achieved rapidly with this dosage without producing deep sedation. However, only limited success has been achieved with the use of intravenous di-phenylhydantoin in status epilepticus in man. 2,6,7 Controversy exists in the reported effects of the drug in stopping experimental seizures in animals. 8,9 In an effort to understand the reasons for failure or

Anemia in obstetrics and gynecology: An evaluation of therapy with parenteral iron

A survey of the causes for a lowered hemoglobin concentration in obstetric and gynecologic patients indicated that the leading causes were acute blood loss, chronic blood loss, frequent pregnancies with iron depletion, or some combination of these. A not uncommon cause of apparent lowered concentration was error by the service laboratory.Obstetric patients who received supplementary iron during the antepartum period came to delivery with a higher hemoglobin level than did patients who had received no iron. When the iron requirements of pregnancy were routinely supplied intramuscularly with iron-dextran, the hematologic improvement was not significantly greater than when ferrous gluconate was given orally. The intramuscular route of administration, however, seemed of considerable value for treating the severely iron-deficient patient to insure maximal response late in pregnancy and subsequently to correct promptly and completely depleted iron stores. While the use of saccharated iron oxide given intravenously was frequently associated with distressing reactions, iron-dextran given intramuscularly produced only transient local soreness.In gynecologic patients with severe iron deficiency anemia as the result of chronic hypermenorrhea, therapy with iron-dextran resulted in rapid correction of the deficit in circulating hemoglobin so that operation usually could be safely performed at the end of 3 weeks without prior transfusion therapy. Similar prompt hematologic improvement was obtained during the puerperium in patients who were anemic as the result of hemorrhage.The calculation of dosage and the method of injection of iron-dextran have been discussed, as have been the indications for blood transfusions and for iron replacement therapy.Since this study was started the use of blood for transfusions but not the amount of blood cross-matched has dropped markedly. In spite of this sharp decrease occasional severe transfusion reactions have not been entirely avoided.