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PubMed1984

[Heparin level and coagulation potential after subcutaneous injection of 7500 international units of heparin calcium].

A dosage of 7500 IU heparin calcium (Calciparin) was administered subcutaneously twice daily in 15 probands. Prior to and after the 1st and 7th injection heparin levels were determined in plasma and coagulation studies were done. The highest heparin levels were found around 4 hours after the injection. They were significantly higher after the 7th injection than after the 1st. Values decreased markedly after 8 hours. After 10-12 hours they approached the initial values, however remained significantly increased. The appropriate changes were seen in activated partial thromboplastin time, thrombin time and reaction- and clotting time in the thrombelastogram. Activity and concentration of antithrombin III decreased by about 10%. Fibrinogen and platelets remained largely unaffected. The results show that twice daily subcutaneous injections of 7500 IU heparin calcium are able to close the anticoagulation gap in plasma which occurs with administration of twice 5000 IU between two injections.

Adult↗
PubMed1990

[Subcutaneous injection of desmopressin (DDAVP) for increasing factor VIII and von Willebrand factor in plasmapheresis].

Desmopressin (DDAVP) is an effective tool for increasing factor VIII (FVIII)/von Willebrand factor (vWF) in normal subjects and in patients with haemophilia A and von Willebrand's disease. There are a few studies utilizing DDAVP to increase the FVIII/vWF yield in plasmapheresis donors. In these studies, DDAVP was given either by intranasal administration or intravenous infusion. The aim of our pilot study was to investigate the subcutaneous (s.c.) injection of DDAVP in combination with double bag plasmapheresis. 8 donors with blood group A and 5 with O were given 0.4 micrograms/kg body weight DDAVP as a s.c. injection 30 min prior to the first donation. FVIII increased 3.7 and ristocetin cofactor 2.5 the initial value in the donors. In the plasma bags, a 3 (1st bag) and 3.5 (2nd bag) fold higher FVIII level was found, when compared with baseline levels. There was only a mild decrease of blood pressure, and serious adverse effects were not observed. Our data suggest that s.c. DDAVP may be more effective and especially suited for increasing FVIII/vWF yield in plasmapheresis donors.

Blood Donors↗
PubMed2000

The pharmacokinetics of morphine and morphine glucuronide metabolites after subcutaneous bolus injection and subcutaneous infusion of morphine.

AIMS: To investigate the pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) in healthy volunteers after the administration of morphine by subcutaneous bolus injection (s.c.b.) and subcutaneous infusion (s.c. i.) over 4 h, and to compare the results with the intravenous bolus (i.v.) administration of morphine. METHODS: Six healthy volunteers each received 5 mg morphine sulphate by i.v., s.c.b. and short s.c.i. over 4 h, on three separate occasions, in random order, each separated by at least 1 week. Plasma samples were assayed for morphine, M6G and M3G. RESULTS: After i.v. morphine, the concentrations of morphine, M6G and M3G and their pharmacokinetic parameters were similar to those we have observed previously, in other healthy volunteers (when standardized to nmol l- 1, for a 10 mg dose to a 70 kg subject). After s.c.b. morphine, similar results were obtained except that the median tmax values for morphine and M3G were significantly longer than after i.v. morphine (P< 0.001 and P< 0.05, respectively), with a trend to a longer tmax for M6G (P = 0. 09). The appearance half-lives after s.c.b. morphine for M6G and M3G were also significantly longer than after i.v. morphine (P = 0.03 and P< 0.05, respectively). Comparison of log-transformed AUC values indicated that i.v. and s.c.b. administration of morphine were bioequivalent with respect to morphine, M6G and M3G. In comparison with i.v. morphine, morphine by s.c.i. was associated with significantly longer median tmax values for morphine (P< 0.001), M6G (P< 0.001) and M3G (P< 0.05), and the mean standardized Cmax values significantly lower than after both i.v. and s.c.b. morphine (morphine P< 0.001, M6G P< 0.001 and M3G P< 0.01 for each comparison). Comparison of log-transformed AUC values after i.v. and s.c.i. morphine indicated that the two routes were not bioequivalent for morphine (log-transformed AUC ratio 0.78, 90% CI 0.66-0.93), M6G (0.72, 90% CI 0.63-0.82), or M3G (0.65, 90% CI 0.54-0.78). A small stability study indicated no evidence of adsorptive losses from morphine infused over 4 h using the infusion devices from the study. CONCLUSIONS: Although bioequivalence was demonstrated between the s. c.b. and i.v. routes of morphine administration, the bioavailabilities of morphine, M6G and M3G after s.c.i. were significantly lower than after i.v. administration. However, despite this, the study demonstrates that the subcutaneous route is an effective method for the parenteral administration of morphine.

Adult↗
PubMed1980

Responses of mouse spleen morphology to the growth of subcutaneously injected virally transformed cells.

The changes in the fractional volume of six structural components in the spleens of Balb/C mice injected with Herpes simplex virus Type 2-transformed cells (H238 tumor cells) were quantitated during progressive tumor growth. Spleen stereology was performed at three time intervals during the early stages of tumor development. The results revealed that the volume of the compact myeloid tissue and reaction center of lymphoid nodules increased about four- to five-fold from 10 to 33 days after H238 tumor cell injection. A progressive increase was also seen in the red pulp volume. Although an increase in volume of the marginal zones around the lymphoid nodules was evident early during the test period, by day 33 the mean value was similar to the control value. These results indicate that the spleen undergoes significant morphological changes in three splenic components during progressive growth of a tumor produced by subcutaneous injection of a virally-transformed cell line.

Animals↗
PubMed2002

Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long-acting preparation and milk residues following a single subcutaneous injection.

Separate groups of goats were used to determine drug depletion patterns in serum (n=10), tissue (n=20) and milk (n=8) following a single intramuscular (i.m.) dose of 20 mg/kg of a long-acting oxytetracycline (OTC) formulation (Liquamycin LA-200). Milk residues were also determined following a subcutaneous (s.c.) administration of the same product at the same dose. Serum samples were taken for 24 h post-treatment and tissues (fat, liver, kidney, muscle and injection site) collected at 4, 7, 14, 21 and 28 days following injection. Milk from lactating goats was collected every 12 h for 8 days following both the i.m. and s.c. treatments utilizing an intervening 5-week washout period. Residues in serum and tissue were measured using a microbial inhibition assay, while milk residues were measured using both a microbial inhibition assay and a validated HPLC method. The serum pharmacokinetic parameters of OTC in goats were determined, with a mean AUC=67.4 microg h/mL, mean terminal half-life=14.4 h, and apparent clearance=0.33 L/kg h. Tissue half-lives could not be determined with confidence because the collection times provided only two points at which residues could be measured for most tissues. Oxytetracycline residues in all goat tissue samples measured less then cattle tissue tolerance by 96 h postdosing. One-compartment model describing milk depletion data for i.m. and s.c. dosing had terminal slope half-lives of 20.1 and 36.1 h, respectively. By 96 h post-treatment none of the milk samples contained OTC residues in excess of the cattle milk tolerance (0.3 p.p.m.). For both milk and tissue, the upper-bound 99% confidence intervals for the samples taken from goats 96 h postdosing were lower than approved cow milk and tissue tolerances.

Animals↗
PubMed1990

Lack of evidence for the size principle of selective vulnerability of axons in toxic neuropathies. I. The effects of subcutaneous injections of 2,5-hexanedione on behavior and muscle spindle function.

2,5-Hexanedione (HD) produces a central-peripheral distal axonopathy. It has been suggested that agents which produce this type of axonopathy show a predilection to the largest diameter fibers. This has been based primarily on morphological data. However, electrophysiological evidence and some clinical and morphological data suggest that this may not be the case. In particular, in acrylamide neuropathy, muscle spindle primary afferents do not show this selectivity, as well as autonomic fibers. This study was carried out to determine whether the largest diameter axons were selectively vulnerable to HD. We found that subcutaneous injections of HD in cats produced a dose-dependent increase in behavioral deficits such as contact placing, stepping, and locomotion. There was also a dose-dependent decrease in the position sensitivity of muscle spindle primary and secondary endings. However, the secondary endings, which are innervated by smaller axons, were affected prior to the primary endings. Also, the velocity sensitivity of the primary endings was depressed at a similar time frame as the position sensitivity of these same endings. These data are consistent with the hypothesis that the caliber of the axon is not the only determinant of the selective vulnerability of axons in distal axonopathy.

Animals↗
PubMedDate not supplied

Fasciitis complicating subcutaneous injection of interferon beta.

Data pertaining to 65 patients treated at the Health Sciences Center Hepatology Research Unit in Winnipeg, Manitoba describing local complications related to subcutaneous interferon (IFN) injection administered to treat hepatitis C virus infection are presented. Nine patients experienced local erythematous reactions at the injection region. No life-threatening complications were identified. One case of fasciitis complicating IFN beta injection - a complication not previously reported - was successfully managed with surgical debridement and antibiotic therapy. This case is a dramatic example of why sterile technique during infections must be adhered to.

Adult↗
PubMed1983

[Fatal pneumopathy linked to subcutaneous injections of liquid silicone into soft tissue].

The case of a 23-year old transsexual male who developed a lethal lung disease 48 hr after a 1 l subcutaneous silicone fluid injection is reported. Histologic examination showed optically empty oil red O negative vacuoles in several specimens, and particularly in the lungs; refractile particles of silicium were also found. We identified the material as silicium, and evaluated its quantity in tissues by atomic absorption and spectrometric and toxicological analysis. Experimental studies and rare human accidents suggest that silicone fluid is transported by migrating phagocytes, thereby explaining lymph node, spleen, liver, adrenal and lung deposits. In our patient's report, we added gradual blood contamination to explain the progressive development of respiratory failure with the severity of the respiratory disorder linked to the massive dose injected. Massive silicone blood embolization could be excluded because of the interval between the injection and emergence of the first clinical signs.

Adult↗
PubMed1999

Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers.

OBJECTIVE: To assess the absolute bioavailability of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands) after a single SC injection. DESIGN: Randomized, crossover, pharmacokinetic study. SETTING: Phase I clinical research unit. PATIENT(S): Nineteen healthy female volunteers of reproductive age. INTERVENTION(S): Two separate injections of 0.25 mg of ganirelix were given, one subcutaneously and one intravenously, with a washout period of 1 week between injections. Blood samples were taken for assessment of serum ganirelix concentrations, and blood pressure, heart rate, and adverse events were monitored. MAIN OUTCOME MEASURE(S): Pharmacokinetic parameters. RESULT(S): Fifteen subjects were evaluated. The mean concentration-time profile after SC administration was comparable to that after IV administration. The mean (+/- SD) peak concentration and time of occurrence after SC administration were 14.8+/-3.2 ng/mL and 1.1+/-0.3 hours, respectively. The mean (+/- SD) half-lives after IV administration and SC administration were highly similar (12.7+/-3.7 hours and 12.8+/-4.3 hours, respectively). Mean (+/- SD) AUC0-infinity (area under the concentration-time curve) values of 105+/-11 ng/mL x hours and 96+/-12 ng/mL x hours were calculated for IV administration and SC administration, respectively, resulting in an absolute mean (+/- SD) bioavailability of 91.3%+/-6.7%. Both treatments were well tolerated. CONCLUSION(S): Ganirelix is absorbed rapidly and extensively after SC administration, resulting in a high absolute bioavailability of >90%.

Adult↗
PubMed1985

Fate of porcine and human insulin at the subcutaneous injection site. II. In vitro degradation of insulins in the subcutaneous tissue of the rat.

We compared the in vitro degradation of porcine and human insulin in the subcutaneous tissue of rat. The insulin degrading activity was largely confined to the 160000 X g supernatant fraction of subcutaneous tissue. The degradation of human insulin was approximately half that of porcine insulin in the supernatant fraction. The degradation of porcine insulin in subcutaneous tissue was inhibited by bacitracin, leupeptin, phosphoramidon, and Z-Gly-Pro-Leu-Gly, though the human insulin degradation was not. The degradation of both insulins was accelerated by glutathione. While the proteolytic enzyme activities of cathepsin-B and collagenase-like peptidase were detectable in subcutaneous tissue, chymotrypsin, elastase, kallikrein, alpha-thrombin, and trypsin activities were almost negligible. These in vitro studies suggest that human insulin is comparatively stable against proteolytic enzymes, probably collagenase-like peptidase or cathepsin-B, in the subcutaneous tissue, which support the in vivo evidence.

Animals↗
PubMed2001

Comparison of intradermal and subcutaneous injections in lymphatic mapping.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma, with its intradermal (ID) injection, has a higher success rate than SNB for breast cancer, which is typically performed with a subcutaneous (SC) or peritumor injection. It is hypothesized that this is in part due to a slower transit time of lymphatic mapping agents through the parenchymal lymphatics of the breast. No study has investigated differences in transit time between different tissues to account for this clinical observation. The goal of the study was to compare transit time between ID and SC injections with common agents used in lymphatic mapping. METHODS: Four injection sites on five domestic pigs were used. Sites were bilateral and included cervical, forelimb, hindlimb, and flank areas. Agents included technetium sulfur colloid (Tc99, filtered and unfiltered), isosulfan blue (IB) dye, and fluorescein (FL) dye. At each site both ID and SC injections were made and the transit time to reach the sentinel node was recorded. The transit time differences were calculated per centimeter distance from the draining lymph node basin. RESULTS: Sentinel nodes were identified draining all sites and found to be hot, blue, or fluorescent (using a Wood's lamp for identification). The cervical and forelimb injection sites drained to the same cervical lymph node basin and both SC and ID injection sites drained to the same sentinel node. Similarly, the hindlimb and flank injection sites both drained to inguinal lymph node basins. The slowest transit time occurred with Tc99 injected SC and the fastest occurred with Tc99 injected ID, whereas both FL dye and IB traveled rapidly to the sentinel node whether injected SC or ID. Large differences were found using unfiltered Tc99 depending on its injection ID (2.7 s/cm +/- 0.5) vs SC (249 s/cm +/- 14.7, P = 0.008). CONCLUSIONS: Tc99 ID injections were significantly faster than SC injection. The slowest and fastest SC injection agents were unfiltered Tc99 and IB, respectively. Dermal injections provide faster transit of lymphatic agents and may improve the identification rate when applied to patients with breast cancer.

Animals↗
PubMed2003

Bioavailability of hCG after intramuscular or subcutaneous injection in obese and non-obese women.

BACKGROUND: Obese women require higher gonadotrophin doses for ovarian stimulation and to trigger ovulation. The bioavailability of a drug is affected by its route of administration. Herein, the bioavailability of hCG was compared after intramuscular (i.m.) or subcutaneous (s.c.) injection in obese and non-obese women. METHODS: Twenty four Chinese women, 12 with a body mass index (BMI) >/==" BORDER="0">28 kg/m(2) and 12 with a BMI of 20-25 kg/m(2) were recruited as the obese and non-obese groups respectively. A single hCG injection was given intramuscularly on one occasion, and subcutaneously on a second occasion, separated by 4 weeks. Blood samples were taken at intervals for the pharmacokinetic study of hCG. RESULTS: Examination of the hCG plasma concentration-time curve showed the area under the curve (AUC) and maximum concentration (C(max)) of hCG to be significantly higher after i.m. injection than after s.c. injection in both the obese and non-obese groups. However, the AUC and C(max) values in obese women were significantly lower than in non-obese women, irrespective of whether i.m. or s.c. dosing was employed. CONCLUSIONS: Intramuscular dosing of hCG provided better bioavailability than s.c. dosing, but bioavailability was significantly less in obese women than in non-obese women.

Adult↗
PubMed1980

Vesicle targeting: timed release and specificity for leukocytes in mice by subcutaneous injection.

When unilamellar vesicles were administered subcutaneously in mice, the half-time for the destruction of the vesicles varied from 12 to 600 hours, depending on their composition. The vesicles tested consisted of distearoyl phosphatidylcholine, cholesterol, and certain sugar and amino-sugar derivatives of cholesterol. Vesicle with amino-sugar derivatives showed the greatest longevity and became localized with high specificity in aggregates of polymorphonuclear leukocytes. A substantial delay between the time that the vesicles broke open and the time that labels contained in the vesicles were excreted suggests that the vesicles undergo endocytosis before destruction.

Animals↗
PubMed1975

Cellular and humoral immune responses in mice. II. Effect of intraperitoneal or subcutaneous injection of carrier of anti-hapten antibody and delayed hypersensitivity responses.

The subcutaneous (s.c.) injection of sheep red blood cells (SRBC) without adjuvant into mice preferentially induced delayed hypersensitivity (DH) reaction, as measured by footpad swelling, while intraperitoneal (i.p.) measured by the haemagglutinin test. Under these conditions, the properties of the helper activities of thymus-derived (T) cells for humoral responses were examined, in association with the features of the DH response, by measuring the anti-hapten and anticarrier antibody responses after a booster injection of trinitrophenylated (TNP) SRBC and by changing the combination of doses and injections routes of the carrier and the hapten-carrier conjugates. When mice were presensitized with i.p. injections of SRBC and boosted with i.p. injections of TNP-SRBC, the anti-TNP antibody production was maximally enhanced by presensitization with a low dose of SRBC, and gradually abolished with higher doses of SRBC for pre-sensitization. In the latter case, anti-SRBC antibody production was increases with increasing doses of SRBC..

Animals↗
PubMed1998

Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.

The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the ability to avoid Fe deficiency nevertheless appeared to be the same in both breeds.

Administration, Oral↗