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

A pharmacokinetic study with [3H]des-enkephalin-gamma-endorphin (3H-DE gamma E) was performed in rats after the intravenous, subcutaneous and intramuscular route of administration. Disappearance of non-metabolized 3H-DE gamma E 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 X 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 X min-1 X 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-DE gamma E 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 DE gamma E 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 DE gamma E might be more effective in displaying CNS activity than the intramuscular route.     

Accumulation of gentamicin in biological fluids, organs and tissues during regional lymphotropic therapy with antibiotics

Gentamicin distribution in biological fluids, organs and tissues, lymph nodes was studied on 70 dogs. Three administration routes were compared: lymphotropic, intramuscular and regional subcutaneous. The lymphotropic route for the drug administration was recommended not long ago. It was shown that the lymphotropic route provided the antibiotic accumulation mainly in some of the abdominal organs as compared to intramuscular administration. Regional lymphotropic administration of the antibiotic to the experimental animals resulted in higher gentamicin levels in the regional lymph nodes and regional organs as compared to the levels observed after the antibiotic regional subcutaneous administration in the same doses.     

Management of severely brittle diabetes by continuous subcutaneous and intramuscular insulin infusions: evidence for a defect in subcutaneous insulin absorption.

Severely brittle diabetes is defined as a rare subtype of insulin-dependent diabetes with wide, fast, unpredictable, and inexplicable swings in blood glucose concentration, often culminating in ketoacidosis or hypoglycaemic coma. To assess the role of inappropriate type, amount, or timing of insulin treatment and the route of administration as a cause of severe brittleness six patients with continuous subcutaneous insulin infusion, which provides a high degree of optimisation of dosage with exogenous insulin in stable diabetics. The glycaemic control achieved during continuous subcutaneous insulin infusion was compared with that during continuous intramuscular insulin infusion. Six patients with non-brittle diabetes were also treated by continuous subcutaneous insulin infusion. These patients achieved the expected improvement in glycaemic control (mean +/- SD plasma glucose concentration 5.1 +/- 2.3 mmol/l (92 +/- 41 mg/100 ml)), but not the patients with brittle diabetes remained uncontrolled with continuous subcutaneous infusion (13.6 +/- 5.8 mmol/1 (245 +/- 105 mg/100 ml) compared with 10.3 +/- 4.1 mmol/l (186 +/- 74 mg/100 ml) during treatment with optimised conventional subcutaneous injections). During continuous intramuscular infusion, however, glycaemic control in five of the patients with brittle diabetes was significantly improved (7.7 +/- 2.6 mmol/l (139 +/- 47 mg/100 ml). The remaining patient with brittle diabetes, previously safely controlled only with continuous intravenous insulin, did not respond to continuous intramuscular infusion. It is concluded that in five of the six patients with brittle diabetes studied here impaired or irregular absorption of insulin from the subcutaneous site played a more important part in their hyperlability than inappropriate injection strategies. This absorption defect was presumably bypassed by the intramuscular route.     

Divided dose intramuscular regimen and single dose subcutaneous regimen for chloroquine: plasma concentrations and toxicity in patients with malaria.

Adults with malaria in Sri Lanka were treated with parenteral chloroquine diphosphate, either 2.5 mg base/kg intramuscularly at 0, 1, 12, 13, 24, and 25 hours or 5 mg base/kg subcutaneously at 0, 12, and 24 hours. Both regimens were completed with oral chloroquine phosphate, 5 mg base/kg, at 36 and 48 hours. Mean peak chloroquine concentrations in the first 12 hours, which were 0.5 (range 0.3-0.6) mg/l (1.4 (0.9-1.7) mu mol/l) [corrected] with the intramuscular regimen and 0.3 (0.2-0.4) mg/l (1.0 (0.7-1.3) mu mol/l) [corrected] with the subcutaneous regimen (p less than 0.05), were reached in median times of 90 (65-90) minutes and 30 (30-60) minutes respectively (p less than 0.05) after the start of treatment. The mean area under the plasma concentration curve for the first 12 hours was 1.4 (0.9-2.1) mg/l.h (4.5 (2.8-6.4) mu mol/l.h) [corrected] after intramuscular administration and 1.8 (0.8-2.3) mg/l.h (5.7 (2.7-7.2) mu mol/l.h) [corrected] after subcutaneous administration (p greater than 0.1). Mean maximum plasma concentrations were higher after intramuscular administration (0.6 (0.4-0.8) mg/l (1.7 (1.3-2.5) mu mol/l)) [corrected] than after subcutaneous administration (0.4 (0.4-0.5) mg/l (1.3 (1.3-1.5) mu mol/l)) [corrected] (p less than 0.05), but both regimens produced satisfactory plasma profiles. Chloroquine resistance was found in the only case of Plasmodium falciparum malaria. Chloroquine is absorbed rapidly after divided dose intramuscular injection and single dose subcutaneous injection and does not cause hypotension or neurotoxicity in adults. Similar regimens should be evaluated in children before the parenteral use of this drug is abandoned.     

H-Pro-[3H]Leu-Gly-NH2: Plasma Profile and Brain Uptake Following Subcutaneous Injection in the Rat

Following subcutaneous injection of the tripeptide H-Pro-[3H]Leu-Gly-NH2 ([3H]PLG) in rats, the profile of intact peptide and its radioactively labeled metabolites was examined both in plasma and in brain tissue. [3H]PLG and metabolites were determined in trichloroacetic acid extracts by reverse-phase paired-ion HPLC. Maximal plasma levels of unmetabolized PLG were reached 6-8 min after administration, after which they decreased with an elimination half-life of 20 min. The uptake of [3H]PLG in the brain ranged from 0.0013% to 0.0017% of the administered dose per g tissue at 6-30 min following subcutaneous injection. After comparing these results with our previous findings with intravenous injection of [3H]PLG, it seemed likely that the subcutaneous route of administration might be more effective in eliciting CNS effects of PLG than the intravenous route of administration. The metabolite profiles in plasma and brain point to an initial cleavage of PLG at the NH2-terminal side and a very rapid degradation of the peptide intermediate H-Leu-Gly-NH2.     

Distribution of Penicillin G in Serum and Tissue Cage Fluid in Cattle*

The penetration of penicillin into tissue cage fluid (TCF) in calves was studied after intravenous and intramuscular injection. The penicillin concentrations in TCF were lower than in serum and maximum was reached much later. Intravenous injection of benzyl-penicillin gave significantly higher levels in TCF than intramuscular injection. The penetration after procaine penicillin was very slow. The results showed that the serum peak rather than the area under curve determines the penetration of penicillin. Repeated intramuscular injections of benzylpenicillin and procaine penicillin caused an accumulation of penicillin in TCF. Similar levels were however reached by one single intravenous injection. The clinical counterparts to the used tissue cage model are abscesses. It was concluded that if high penicillin concentration are desireable in such foci, the drug must be given in a way that gives as high serum peaks as possible.     

The immune response of brown trout (Salmo trutta L.) to injection with soluble antigens.

The immune response of brown trout (Salmo trutta) to horse serum and keyhole limpet haemocyanin was studied. Intraperitoneal and intramuscular injections were used, with and without adjuvant, in 209 fish. Complement-fixing antibodies (CFA) and precipitins were produced to both antigens. CFA were detected after 8 days to haemocyanin and after 13 days to horse serum. Maximum CFA titres to a single intraperitoneal injection of horse serum or haemocyanin were reached at 44 and 43-46 days respectively. Precipitins to a single injection of haemocyanin given intraperitoneally were detected after 19 days using gel diffusion. Similarly using the intramuscular route they were detected after 22 days. However, using counter-current electrophoresis, precipitins were detected after 8 days by the intraperitoneal route and after 9 days by the intramuscular. Precipitins to horse serum given intraperitoneally were demonstrated after 22 days by both gel diffusion and counter-current electrophoresis. Fish given 2 intraperitoneal injections of haemocyanin in adjuvant reached maximum CFA titres after 55 days; a 3rd injection on day 56 did not produce a marked increase in titre. Fish given intramuscular injections of haemocyanin in adjuvant showed maximum CFA titres at day 43. After a 3rd injection on day 56, maximum CFA titres were reached between days 92 and 106. Intramuscular injections gave significantly higher titres than those given by the intraperitoneal route. Some fish which showed no precipitins by gel diffusion were positive by counter-current electrophoresis. Precipitating antibodies to haemocyanin migrating in the beta2-gamma1 region were detected by immuno-electrophoresis.     

Measurement of ivermectin concentrations in target worms and host gastrointestinal tissues: influence of the route of administration on the activity against resistant Haemonchus contortus in lambs

The influence of the administration route on the relationship between efficacy and ivermectin concentration profiles achieved in the bloodstream, the gastrointestinal mucosal tissues/fluid contents and within a target abomasal parasite (Haemonchus contortus) was evaluated in lambs. Twenty-six (26) parasitized lambs were assigned into three experimental groups: untreated (control) and ivermectin treated by the subcutaneous and intraruminal route at 0.2mg/kg. Blood samples were collected between 0 and 15 days post-treatment (plasma disposition study). Four animals from each group were sacrificed at day 3 post-treatment. Mucosa and content samples from abomasum and small intestine and adult specimens of H. contortus were collected. Drug concentrations were measured by HPLC. Individual fecal egg counts were evaluated at -1, 3 and 15 days post treatment. Post-mortem examination was done at day 15 post-treatment. Adult nematodes recovered from the digestive tract were counted and identified by species. Ivermectin plasma availability was higher (P<0.05) after the subcutaneous administration (129 ng.d/ml) compared to the intraruminal treatment (58.4 ng.d/ml). However, ivermectin concentrations measured in the gastrointestinal contents were higher in lambs treated by the intraruminal route. The mean ivermectin concentrations achieved (3 days post-treatment) in the abomasal content were 143 ng/g (intraruminal) and 2.53 ng/g (subcutaneous). Ivermectin concentrations were 15-fold higher in H. contortus recovered from intraruminally treated lambs. Whereas the subcutaneous administration reduced the number of adult nematodes from 4376 to 1300, the number of adult nematodes after the treatment with ivermectin given by the intraruminal route was 206 (P<0.05). The higher ivermectin concentrations achieved in the digestive tract shortly after the intraruminal treatment may account for the observed enhanced efficacy compared to the parenteral administration against parasites of reduced susceptibility.     

人tPA信号肽和Yersinia Pestis保护性抗原F1-V融合基因的构建及其免疫效果观察

为获得含有鼠疫F1和V抗原编码基因以及人tPA信号肽基因的重组质粒tPA-pVAX1/F1-V,并测定其诱导特异性免疫应答的能力, 用PCR扩增鼠疫菌F1和V编码基因,分别与pGEM-T连接测序,构建pVAX1/F1-V融合重组质粒.PCR扩增tPA信号肽片段并将其插入到F1-V的上游,构建tPA-pVAX1/F1-V融合重组质粒;转染COS-7细胞,Western blot法鉴定目的蛋白的表达.重组质粒tPA-pVAX1/F1-V加GM-CSF佐剂免疫BALB/c小鼠,观察免疫效果.400个LD50强毒鼠疫菌皮下攻毒观察保护率.结果表明,tPA-pVAX1/F1-V在COS-7细胞中表达;免疫鼠体内产生特异性抗体;抗体亚型分析、细胞因子等指标的测定表明,所构建DNA疫苗以诱发Th1型免疫为主;&#61472;攻毒保护率达90%.结果提示,已成功构建F1-V融合蛋白真核表达载体tPA-pVAX1/F1-V,且具有诱导特异性细胞免疫和体液免疫应答的能力, 对强毒鼠疫菌皮下攻毒有一定的保护效力,为鼠疫菌新型疫苗研制奠定了基础.     

催产素肌注用于治疗产后乳汁淤积的相关研究

目的:通过肌注催产素治疗产后乳汁淤积,研究产后乳汁淤积的原因、临床症状及治疗。方法:回顾性分析我院2009年2月-2012年2月收治发生乳汁淤积患者200例的临床资料,随机分为实验组和对照组,各100例,实验组采取催产素肌注治疗,对照组采取按摩加热敷常规治疗。结果:两种患者均治疗3-5d后,实验组治愈67(67.00%)例,有效30(30.00%)例,无效3(3.00%)例,总有效率为97.00%,明显优于对照组,通过治疗30min及24h观察有效率发现实验组30min40(40.00%)例乳房胀痛及乳腺结节减轻,24h后97(97.00%)例乳房胀痛及乳腺结节减轻,用药后两侧乳腺导管直径分别对比,P<0.05,实验组治疗前后同侧乳腺导管直径对比,P<0.05,对照组治疗前后差异不明显,可见,用药后实验组乳腺导管扩张。结论:肌注催产素可以有效预防治疗产后乳汁淤积,出现乳腺肿胀症状,及时肌注,可以预防乳汁淤积出现。     

Inhibition of established subcutaneous and metastatic murine tumors by intramuscular electroporation of the interleukin-12 gene

In vivo electroporation (EP) of the murine interleukin-12 (IL-12) gene in an expression plasmid (pIL-12) was evaluated for antitumor activity. EP transfer of pIL-12 into mouse quadriceps muscles elicited significant levels of serum IL-12 and interferon-gamma. Intramuscular EP of pIL-12 resulted in complete regression or substantial inhibition of 38C13 B-cell lymphoma, whereas pIL-12 delivered by gene gun or intramuscular injection without EP showed little therapeutic effect. Impressive antitumor activity by intramuscular EP was also demonstrated in animals with advanced malignant disease. At day 14 after 38C13 tumor inoculation, all animals were found to carry large tumors and to have metastases; without treatment, most died within a week. A single intramuscular EP of pIL-12 resulted in regression of 50% of large subcutaneous tumors and significantly prolonged the lifespan of these animals. Moreover, animals that were previously cured of 38C13 tumors by in vivo EP treatment significantly suppressed tumor growth when challenged 60 days later. In vivo EP of the IL-12 gene was also effective in suppressing subcutaneous and lung metastatic tumors of CT-26 colon adenocarcinoma and B16F1 melanoma cells. Together, these results show that intramuscular electrotransfer of the IL-12 gene may represent a simple and effective strategy for cancer treatment.     

Experimental transmission and tissue tropism of white spot syndrome virus (WSSV) in two species of lobsters, Panulirus homarus and Panulirus ornatus

The susceptibility of two species of lobsters, Panulirus homarus and Panulirus ornatus to white spot syndrome virus (WSSV) was tested by oral route and intramuscular injection. The results revealed that these lobsters were as highly susceptible as marine shrimp when the WSSV was administered intramuscularly. The WSSV caused 100% mortality in both Panulirus homarus and Panulirus ornatus, at 168 and 120 h, respectively, after intramuscular injection and failed to cause mortality when given orally. The presence of WSSV in moribund lobsters was confirmed by single-step and nested PCR, Western blot, histology, and bioassay test. It was found in eyestalk, gill, head muscle, tail muscle, hemolymph, appendages, and stomach. In lobsters with oral route infection, all tested organs except stomach and head muscle was negative for WSSV by nested PCR at 120 h post-inoculation. The stomach and head muscle was positive by nested PCR at 120 h p.i., but negative at 168 h p.i. Western blot analysis was negative in all the tested organs of both species of lobster at 120 h post-inoculation by oral route.     

The use of intramuscularly administered methyl-TRH to evaluate the pituitary-thyroid axis.

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.     

Pharmacokinetic prediction of the efficacy of using sisomicin in wound infections

The pharmacokinetics of sisomicin in the blood, infection foci and urine of patients with wound infections was studied comparatively. Higher blood levels of the antibiotic after intravenous injection as compared to those after intramuscular injection provided its more intensive penetration into the tissues of the wound edges and bottom. After intravenous injection the sisomicin concentration in the tissues was sufficient for inhibition of the strains of Staphylococcus, E. coli and Ps. aeruginosa detected in the patients, while after intramuscular injection the antibiotic levels were sufficient only for inhibition of the first two causative agents. Comparison of the data on the sisomicin pharmacokinetics in the blood and tissues of the wounds provided the characteristics of the level of the drug penetration into the focus of the infection ("therapeutic availability"). Since the levels of sisomicin in the blood and infection foci were highly variable in different individuals. It is recommended that the antibiotic be used under the control of its concentrations in patients. It was shown that the data on the sisomicin renal excretion might be used for the purposes of the pharmacokinetic control.     

The metabolism of retinyl methyl ether in the rat in vivo

1. Retinyl methyl ether was converted into vitamin A in vitamin A-deficient rats regardless of whether administered by oral, intraperitoneal, intramuscular or subcutaneous route; intramuscular administration seemed to be the best for conversion as well as storage. 2. Significantly, unchanged retinyl methyl ether was also found in the liver after oral administration but not after administration by other routes. 3. Oral administration of 1mg of retinyl methyl ether led to a progressive increase in liver vitamin A with time reaching a value of 16% of administered dose after 24h. No retinyl methyl ether was detectable in liver at any time-interval in this experiment. 4. Conversely, oral administration of 4mg of retinyl methyl ether/day for 4 days led to the accumulation of 25% of the dose as unchanged retinyl methyl ether in the liver 1 day after the last dose; however, it was gradually but completely converted into vitamin A over a period of 18 days. 5. The significance of these findings with special reference to the fundamental metabolism of vitamin A, the site of conversion of retinyl methyl ether into vitamin A, the relative efficiency of various routes of administration and its biological activity are discussed.     

Assessment of MRI Contrast Agent Kinetics via Retro-Orbital Injection in Mice: Comparison with Tail Vein Injection

It is not known whether administration of contrast agent via retro-orbital injection or the tail vein route affects the efficiency of dynamic contrast-enhanced magnetic resonance imaging (MRI). Therefore, we compared the effects of retro-orbital and tail vein injection on the kinetics of the contrast agent used for MRI in mice. The same group of nine healthy female mice received contrast agent via either route. An extracellular contrast agent was infused via the tail vein and retro-orbital vein, in random order. Dynamic contrast-enhanced MRI was performed before and after administering the contrast agent. The contrast effects in the liver, kidney, lung, and myocardium were assessed. The average total times of venous puncture and mounting of the injection system were about 10 and 4 min for the tail vein and retro-orbital route, respectively. For all organs assessed, the maximum contrast ratio occurred 30 s after administration and the time course of the contrast ratio was similar with either routes. For each organ, the contrast ratios correlated strongly; the contrast ratios were similar. The retro-orbital and tail vein routes afforded similar results in terms of the kinetics of the contrast agent. The retro-orbital route can be used as a simple efficient alternative to tail vein injection for dynamic contrast-enhanced MRI of mice.     

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines

The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.     

A Comparison of the Oxytetracycline Preparations Aquacycline® and Terramycin®–100 with Regard to Absorption Characteristics,Local Tissue Reactions and Residues Following Dewlap Injections in Calves

In an experiment with 12 calves, Aquacycline® in a 5 % (OTC-A5) and a 10 % (OTC-A10) solution, was compared with Terramycin®-100 (OTC-C) by injecting 20 mg OTC/kg bwt. of these preparations in the dewlap and monitoring serum concentrations as well as tissue reactions and residues at the site of injection. All 3 preparations resulted in oxytetracycline (OTC) serum concentrations above 0.5 µg/ml of approximately 60 h. During this period, OTC-A5 resulted in a 39 % and OTC-A10 in a 20 % larger area under the serum concentration-time curve, as compared to OTC-C (P < 0.05). The recorded tissue reaction in the form of swelling during the first week following injection of OTC-A5 averaged 72 % of that after OTC-C (P < 0.01), while the mean swelling after OTC-A10 was 81 % of the corresponding value after OTC-C (P < 0.05). The OTC residue levels at the sites of injection were lower after OTC-A5, but none of the preparations resulted in OTC residues exceeding 0.3 mg at 28 days and about 0.15 mg at 42 days after injection. The pathological changes at the site of injection were somewhat more pronounced in those calves which received OTC-C. Accordingly, these results give some support to the claims that Aquacycline® offers advantages with respect to absorption characteristics and tissue tolerance.     

Differences in the Pharmacokinetics of Cocaine in Naive and Cocaine-Experienced Rats

Enhanced cocaine concentrations in brain and blood observed after an intraperitoneal challenge dose in rats exposed to cocaine for 10 days by subcutaneous administration are traced to a change in the absorption process from the site of an intraperitoneal injection to general circulation. This conclusion is reached by three sets of corroborating results: (a) Adipose tissue of rats treated for 10 days with repeat subcutaneous injections of cocaine did not reveal a buildup of cocaine in sufficient concentrations to account for the twofold increase in brain and blood concentrations seen during intraperitoneal administration; (b) administration of the drug by an intravenous route after 10-day cocaine treatment did not show a significant difference between treatment and control groups; (c) nonlinear regression on the intravenous and intraperitoneal data sets using a two-compartment open model indicated a difference in the absorption process but not in the metabolic and blood-brain transfer processes.     

Effects of route of inoculation on the site of development of Caryospora bigenetica (Apicomplexa: Eimeriidae)

The sites of infection by Caryospora bigenetica in Swiss-Webster mice (Mus musculus) were demonstrated after 7 routes of inoculation: oral, intraperitoneal, intravenous, intramuscular, subcutaneous, dermal, and intraocular. All mice exhibited clinical signs of dermal coccidiosis 9 days after inoculation regardless of the inoculation route. Signs included swelling of the facial tissue, footpads, and scrota (male mice). Developmental stages of the parasite were found in the muzzle, tongue, footpad, lumbar subcutaneous tissue, biceps femoris muscle, conjunctiva, and eye; the latter 3 sites represent new sites of development. The site of development of the parasite in the host tissue was independent of experimental inoculation route.