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At least 19 recordsLinked to original sources
PubMed2002

Improvement of the enzymatic stability of a cytotoxic T-lymphocyte-epitope model peptide for its oral administration.

Oral administration of peptide antigens, to provide proper mucosal and/or systemic immunity, is largely ineffective. This is mainly due to the very small quantity of antigen that survives degradation in the intestine and that crosses the intestinal absorption membrane. The present study focuses on the improvement of the enzymatic stability of a 13 amino acid long peptide containing a cytotoxic T-lymphocytes (CTL)-epitope. Within this study, it is shown, that simple chemical modification at the N- and C-terminus of the peptide can provide significant stability towards enzymatic attack by intestinal exopeptidases. Around 50% of the modified peptide resisted enzymatic attack on native porcine intestinal mucosa within 3h of incubation at pH 6.8 and 37 degrees C, whereas unmodified control peptide was almost completely degraded within the same time period. Additionally, a mucoadhesive drug carrier matrix with specific inhibitory properties towards luminally secreted endopeptidases has been generated. The incorporation of the simply modified peptide in this delivery system should enhance the amount of biologically active antigen being available at the mucosal site for further presentation to immunomodulating systems. This might open the door for a successful oral immunotherapy.

Administration, Oral↗
PubMed1998

Effect of barbiturate on central pain: difference between intravenous administration and oral administration.

OBJECTIVE: To examine whether the oral administration of barbiturates is of clinical use in a patient with central pain. SETTING: Pain Clinic, Osaka University Medical Hospital, Osaka, Japan. PATIENT: A patient with central pain after loss of his left upper extremity. INTERVENTIONS: A 50-mg dose of intravenous amobarbital, which produced a plasma concentration of 2.5-4.0 microg/ml, was effective in reducing the central pain. Subsequently, doses of 300-400 mg/day were administered orally; these succeeded in achieving similar plasma concentration levels. RESULTS AND CONCLUSIONS: Oral administration of barbiturate did not alleviate central pain, even when the plasma concentration was the same as the effective level in intravenous use. Pharmacokinetic and pharmacodynamic factors more complex than simple plasma concentrations may be involved in producing the difference in the effects.

Administration, Oral↗
PubMed2002

Pharmacokinetics of the active antifungal enantiomer, SCH 42427 (RR), and evaluation of its chiral inversion in animals following its oral administration and the oral administration of its racemate genaconazole (RR/SS).

Genaconazole (SCH 39304) is a potent triazole antifungal agent that is active both orally and topically. Genaconazole is a racemic mixture which contains 50% of the RR (SCH 42427) and 50% of the SS (SCH 42426) enantiomers. The RR isomer accounts for most of the antifungal activity of genaconazole. Serum concentrations of the RR and SS enantiomers were analyzed by a chiral HPLC method which involved extraction of serum with organic solvent followed by separation on a Cyclobond I column and quantification by UV absorbance at 205 nm. The bioavailability and pharmacokinetic profiles of the two enantiomers after oral administration of the racemate (genaconazole) were very similar in cynomolgus monkeys. In rats following dosing with genaconazole, the RR enantiomer had a lower C(max) and a longer t(1/2) than the SS enantiomer, while the AUC(I) values of the two enantiomers were similar. Based on chiral HPLC analysis, there was no evidence for the inversion of the RR to the SR isomer, or of the SS to the SR isomer, indicating that there was no chiral inversion of the RR or SS enantiomers in either species. Genaconazole at 20 mg/kg and the RR (SCH 42427) enantiomer at 10 mg/kg had very similar serum concentration-time profiles and C(max), AUC(I), and t(1/2) values for the RR enantiomer in both rats and monkeys, indicating that the two treatments were equivalent with respect to the bioavailability of the RR enantiomer.

Administration, Oral↗
PubMed1985

[A phase II study of etoposide (NK 171) in small cell lung cancer--comparison of results between intravenous administration and oral administration].

A phase II study of Etoposide (NK 171) was carried out in 13 institutions of the National Chest Hospital Lung Cancer Cooperative Study Group. Twenty-two patients (pts.) were treated by intravenous (i.v.) administration of etoposide, 80 mg/m2/day, for 5 consecutive days, and 25 pts. by oral administration of the same drug, 130 mg/m2/day, for 5 consecutive days. Eight (36.4%) out of 22 evaluable pts. given i.v. etoposide showed partial response (PR) while 7 (28%) out of 25 evaluable pts. given oral etoposide showed PR. Thirteen (41%) out of 32 previously untreated pts. were responders, but only 2 (13%) out of 15 previously treated pts. responded. The average total dose of i.v. etoposide was 664 (368-1552) mg/m2 while that of oral etoposide was 1320 mg/m2, or about double the dose of i.v. etoposide. The major dose-limiting factor was leukopenia (less than 3000/mm3). being observed in 63.6% of the i.v. treated pts. and 31.8% of the orally-treated pts. The oral and i.v. etoposide provided equivalent results. Despite the advantage of the reduced myelotoxicity of oral etoposide, we may recommend that all pts. are treated parenterally at present until the problem of erratic absorption of the oral drug is resolved.

Administration, Oral↗
PubMedDate not supplied

[Antidiabetogenic action of heparin during its oral administration].

Oral heparin given to rats was found to neutralize the hyperglycemic and hypoinsulinemic effects of diabetogenic factor and to produce a protective action by preventing the animals from the diabetogenic action of alloxan. The chronic oral heparin use alleviated the course of severe alloxan diabetes in rats, by contributing to the reduction of hyperglycemic levels, to the elevation of blood insulin concentrations, thus promoting their higher survival.

Administration, Oral↗
PubMed2002

Efficacy of oral administration and oral intake of edible vaccines.

To evaluate whether vaccine administration via intragastric gavage is indicative for the outcome of edible vaccines, mice were orally immunised with ovalbumin (OVA) mixed with or without Vibrio cholerae toxin (CT) in various compositions via various routes: (1) OVA dissolved in saline and intragastrically (IG) administered ('IG'); (2) OVA mixed with food extract and administered IG ('food IG'); (3) food chow absorbed with OVA dissolved in saline and fed to the animals ('food'); and (4) OVA dissolved in saline and administered via drinking bottles ('drinking'). When given to naive mice, 'IG' and 'food IG' but not 'food' or 'drinking' induced anti-OVA IgG1 responses in serum, but oral boost immunisations were necessary. Serum IgA was not induced. Oral boosting of subcutaneously (SC) primed mice enhanced the IgG1 and IgA response in serum regardless of the route of immunisation or the vaccine composition. CT did not dramatically enhance the immune response. All immunisation routes except 'drinking' induced antigen-specific IgA antibody secreting cells (ASC) in the lamina propria of naive mice. But antigen-specific antibody responses in faeces were not observed. We concluded that oral (i.e. IG) administration is distinct from oral intake. The composition of the vaccine (food or saline) did not influence oral administration. We thus suggested that the route of administration greatly influenced the outcome of oral immunisation. Although oral administration is a well-accepted route to test the potentials of oral vaccines, our study demonstrated that it is merely indicative for the effectiveness of edible vaccines. Studies on the feasibility of edible vaccines should thus be performed by eating the vaccine.

Administration, Oral↗
PubMed1985

[UFT concentration in serum and tissues of patients with gynecologic malignant tumors following oral administration].

Oral UFT was given to patients with genital carcinoma prior to surgery. 5-FU, FT and uracil levels in the tumor site were then measured in the surgical specimens obtained. Simultaneous estimates of tissues and plasma 5-FU indicated that the amount of drug in the tumor site (0.227 +/- 0.117 micrograms/g wet weight) had a 6.3-fold increase in concentration compared with that in normal tissues (0.036 +/- 0.019 micrograms/g wet weight) and was approximately 13.4 times that of the peripheral circulation (0.017 +/- 0.007 micrograms/ml). The rate of increase in concentration of tissue 5-FU rose especially in carcinoma of the cervix (0.394 +/- 0.215 micrograms/g), corpus uteri (0.116 +/- 0.042 micrograms/g) and ovary (0.171 +/- 0.047 micrograms/g). In the case of carcinoma of the cervix, the concentration of 5-FU in the tumor site was found to be about 14.1 times higher in invasive carcinoma than in carcinoma in situ. 5-FU concentration in the tumor site showed a still higher level compared with normal tissue after the drug was administered, suggesting an accumulation of 5-FU within the tumor.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Transfer of methyl chloroform, trichloroethylene and tetrachloroethylene to milk, tissues and expired air following intraruminal or oral administration in lactating goats and milk-fed kids.

The distribution of methyl chloroform was determined (MCF), trichloroethylene (TRI) and tetrachloroethylene (PCE) in milk, tissues and expired air by intraruminally administering 0.625 ml kg(-0.75) of an equal-volume mixture of the three compounds to lactating goats. The milk secreted during 24 h after the intraruminal administration contained 1.42 mg of MCF, 1.87 mg of TRI, 6.43 mg of PCE and 0.33 mg of trichloroethanol (TCE). MCF, TRI and PCE appeared in the blood less than 30 min after administration. Oral administration of these chemicals to milk-fed kids showed that at 3.5 h post-administration, the liver contained these chemicals in greatest abundance. The adaptation of milk-fed kids to 3 weeks administration of small amounts of propylene glycol stimulated the metabolic conversion of TRI to TCE. There were linear relationships between the blood concentrations of these chemicals and the expiration rates after oral administration of 0.4 ml kg(-1) of each chemical to milk-fed kids. The expiration rates of MCF, TRI and PCE were 605, 122 and 46 microg min(-1) kg(-1) at 2 microg ml(-1) blood concentrations of MCF, TRI and PCE, respectively. These results suggested that MCF is little metabolized, being most readily exhaled in expired air, while PCE demonstrates the greatest tissue-partitioning, being largely secreted into the milk or retained in the liver. TRI can be extensively metabolized to other compounds such as TCE in milk-fed kids.

Journal Article↗
PubMed1992

[The effect of preoperative oral administration of ranitidine on pH and volume of gastric juice].

The effect of ranitidine, administrated 2 or 4 hours prior to induction of anesthesia, on volume and pH of gastric juice was investigated in patients undergoing elective surgery. Three-hundred mg of ranitidine was administrated orally in 54 patients 2 hours prior to anesthesia and in 50 patients 4 hours prior to anesthesia. The volume and pH of gastric juice were measured immediately after induction of anesthesia. In more than 90% of patients of both groups, volume of gastric juice was smaller than 25 ml and its pH was more than 2.5. Ranitidine 450 mg was administrated orally in 7 patients, and its plasma concentration was measured 2, 4 and 6 hours after administration. In one patient, volume of gastric juice was larger than 25 ml and its pH was less than 2.5. Ranitidine concentration in this patient was below the effective level 2 hours after administration and it was above the level after 4 hours. We concluded that oral administration of ranitidine 300 mg, 4 hours preoperatively, could be more effective to prevent aspiration pneumonitis than when it is given 2 hours preoperatively.

Administration, Oral↗
PubMed2000

Prevention of nephrotoxicity of cisplatin by repeated oral administration of ebselen in rats.

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded

Administration, Oral↗
PubMed1983

Early stages of chemically induced liver carcinogenesis by oral administration of the antihistaminic methapyrilene hydrochloride.

The antihistaminic drug methapyrilene hydrochloride, which induces liver tumors in rats, was administrated orally to female Wistar rats. The animals were killed after 21, 38, 77, 119, 181, and 196 days. The activities of adenosine-5-triphosphatase (ATPase) and gamma-glutamyltranspeptidase (gamma-GT) in the liver were investigated histochemically. At 21 days, a homogeneous decrease of ATPase activity as well as a slight increase of gamma-GT activity was found in the periportal zone. Additionally, after 38 days hepatocellular foci with reappearance of gamma-GT occurred mainly in the periportal zone. After 119 days, foci with increased gamma-GT activity as well as a significant reduction of ATPase activity could be observed predominantly in the periportal region. The size and number of these putative preneoplastic foci were increased according to the time of administration of methapyrilene hydrochloride. After 181 days of methapyrilene hydrochloride treatment three of five animals developed hyperplastic nodules with corresponding alterations of enzyme activities. Methapyrilene hydrochloride-a carcinogen with an unknown mechanism of reaction-produces preneoplastic changes that are analogous to the well known preneoplastic lesions in the liver observed after administration of other carcinogenic agents.

Adenosine Triphosphatases↗
PubMed1987

Pharmacokinetics of norethisterone following its oral administration and by spraying it nasally or sublingually to male bonnet monkeys.

Pharmacokinetic parameters of norethisterone (NET) were studied in eight adult male bonnet monkeys following the administration of a single dose of 300 ug. The animals were crossed over between the following three routes of administration: oral ingestion, nasal and sublingual spraying. The results indicate that NET was readily absorbed by all three routes but the Cmax and AUC of NET were significantly greater by the sublingual route. No significant difference in the t 1/2 alpha or t 1/2 beta was observed between the three routes. These findings suggest that the sublingual route offers the possibility of reducing the effective dose of NET, which is widely used for contraceptive purposes.

Administration, Intranasal↗
PubMed1986

[Determination of piperazine in hen eggs with HPLC following oral administration].

After oral administration of piperazine citrate to hens, this antihelmintic agent appeared unchanged in the eggs. After a therapeutic dose of ca. 0.9 g piperazine citrate per hen, a maximum level of 1.5 mg piperazine/kg egg was found two days after the application. The elimination half-life was 29 h and piperazine was found in the eggs up to 17 days after administration (limit of detection: 1 microgram/kg). Piperazine determination was performed by HPLC of the dansylderivative after clean-up by TLC.

Administration, Oral↗
PubMed1984

Investigations on the detection of mutagenic activity of beef extract in rats after oral administration.

After oral administration of beef extract the body fluids of Aroclor-treated and untreated rats were investigated for mutagenicity using the Salmonella/microsome test. In the stomach contents, the bile and the urine of the animals, mutagenic activity was discovered after S-9 activation. Although the mutagenic substances must have been transported by the blood stream to the excreting organs no increased mutagen-induced his+ revertants were observed in venous blood. Direct-acting mutagens were not detected in the tested body fluids, either in the Aroclor-treated rats or in the untreated ones.

Administration, Oral↗
PubMed1989

[Pharmacokinetics of norethindrone-oxime and norethindrone in rabbits after oral administration].

After oral administration of [3H]-labelled norethindrone-oxime (NETO) or norethindrone (NET) to rabbits, the blood concentrations of NETO and NET were determined by measuring the radioactivity after separation with HPLC. The pharmacokinetic parameters of the compounds were also compared. Experimental results indicate that both NETO and NET were quickly absorbed. Their elimination from blood revealed a fast and a slow phase. One portion of NETO was metabolized to NET, and the remainder was excreted in unchanged form. The amount of NETO and its metabolite, NET, in serum were about equal within 24 hours. The serum concentration-time curves of NETO and NET adequately fitted to a two-compartment model. There was significant difference between NETO and NET in Tmax (P less than 0.05). But no significant differences in other parameters (P greater than 0.05) were observed.

Administration, Oral↗