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PubMedDate not supplied

[Change in interferon status in patients with acute viral hepatitis during intramuscular and rectal administration of genetically engineered alpha-2-interferon].

Viferon500 suppositories representing a combination of recombinant alpha 2-interferon and membrane-stabilizing agents were used in the treatment of adult patients with acute viral hepatitis B. Changes in interferon status of the blood under the effect of reaferon and viferon500 were studied. Both reaferon and viferon500 suppositories were found to stimulate interferon synthesis in patients with acute viral hepatitis B, their stimulating effect correlating with the positive time course of clinical manifestations of the disease. The results permit us recommend viferon500 for the treatment of viral hepatitis in the early period of the icterus in order to prevent the disease progress. Parameters of the interferon system may serve as an objective criterion for assessment of the treatment efficacy.

Acute Disease↗
PubMed1993

Pharmacokinetics of metronidazole after rectal administration in horses.

Five healthy adult mares and 1 gelding were given a single dose (15 mg/kg of body weight) of metronidazole per rectum. After manual evacuation of feces from the rectum, a suspension of crushed tablets and water (40 ml) was administered via a 28-F catheter advanced 30 cm into the rectum. Blood samples were obtained by jugular venipuncture, and metronidazole concentration was measured serially for the 14 hours after drug administration. Mean serum concentration of metronidazole peaked at 4.5 micrograms/ml, 0.83 hour after administration, and decreased to 0.38 microgram/ml, 14 hours after administration. Mean elimination rate constant was 0.23/h, and the harmonic mean elimination half-life was 3.04 hours. Further study is necessary to determine a therapeutic dose regimen for metronidazole administered per rectum.

Administration, Rectal↗
PubMed1994

Measurement of portal systemic shunting by oral and per-rectal administration of [123I]iodoamphetamine, and clinical use of the results.

UNLABELLED: OBJECTIVE. We used a method by which the portal shunt index via the superior mesenteric vein (SI-S) and that via the inferior mesenteric vein (SI-I) could be evaluated simultaneously. The clinical usefulness of the method was studied. METHODS: Scintigraphy was done 3 h after subjects took an enteric-coated capsule containing [123I]iodoamphetamine. At that time, the radionuclide was injected into the rectum. Counts for the lungs and the liver were used to calculate the two shunt indices. RESULTS: The mean SI-S and SI-I tended to be higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis. In cirrhotic patients, the SI-I was higher than the SI-S (p < 0.001). The SI-S and SI-I were both higher in cirrhotic patients with esophageal varices than in such patients without varices (p < 0.05 and < 0.001). The SI-S and SI-I were higher in cirrhotic patients with ascites than in such patients without ascites (p < 0.001 and < 0.01). Correlation between either of these indices and classical indicators of functional reserve was high. The correlation of SI-S with the Child-Turcotte classification and total bilirubin level was higher than the correlation of the SI-I and these indicators of functional reserve. CONCLUSIONS: This method permits assessment of the portal hemodynamics in a relatively noninvasive way, and is clinically meaningful.

Administration, Oral↗
PubMed1988

Hydrolysis of salicyluric acid in intestinal microorganisms and prolonged blood concentration of salicylic acid following rectal administration of salicyluric acid in rats.

The blood concentrations of salicyluric acid and salicylic acid following oral, intravenous, intracecal and rectal administration of salicyluric acid were determined in rats. After oral administration of salicyluric acid, salicyluric acid was rapidly absorbed. Salicylic acid was detected at low concentration. Following intravenous administration of salicyluric acid, salicyluric acid was detected in the blood and was rapidly eliminated. A trace amount of salicylic acid was detected, suggesting that systemic deconjugation of glycine was involved. Furthermore, in vitro incubation of salicyluric acid with contents of the gut showed that the major source of the hydrolysis was the hind gut. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration of salicyluric acid. The blood concentration of salicylic acid was maintained at 2.6-4.0 micrograms/ml from 4 to 12 h following rectal administration of salicyluric acid (10 mg/kg: salicylic acid equivalent). Species difference in the metabolic fate of salicyluric acid in rats and rabbits reported previously is discussed.

Administration, Oral↗
PubMed1989

Chronopharmacokinetic study of valproic acid in man: comparison of oral and rectal administration.

Circadian stage-dependent changes of valproic acid (VPA) kinetics was examined after rectal administration comparing after oral dosing. Eight healthy volunteers took a single oral or rectal dose of VPA 400 mg, in a form of sodium valproate, on two occasions, at 8:30 A.M. or 8:30 P.M. Subjects were synchronized with diurnal activity and nocturnal rest as their usual life under standardized meal conditions. After oral administration, mean total VPA concentrations in plasma were significantly higher in the morning than in the evening during the absorption phase. Cmax tended to be higher, tmax was shorter (P less than 0.05) and absorption rate constant (ka) tended to be larger (0.05 less than P less than 0.1) for VPA in the morning than in the evening, although no difference was demonstrated in other pharmacokinetic values between morning and evening trials. After rectal administration, no significant difference was demonstrated in VPA kinetics between morning and evening trials. The rectal administration might have an advantage to eliminate the time-dependent changes of VPA kinetics. Thus the current practice of giving a rectal dose seems to be justified because the time-dependent changes in VPA kinetics observed after oral administration may be reduced without compromising therapeutic efficacy.

Administration, Oral↗
PubMed1988

Intravenous or rectal administration of sedatives in outpatient oral surgery.

A number of cross-over studies on sedation in outpatient oral surgery investigated the quality of sedation produced by intravenous or rectal administration of diazepam. The sedation methods were equally efficient with a mean dose of 0.24 mg/kg (range 0.1-0.4) for i.v. administration and 0.53 mg/kg (range 0.5-0.6) for rectal administration. Eighty-five per cent of the patients preferred surgery under sedation and local anaesthesia to local anaesthesia alone. The patients preferred the session in which they experienced stronger sedation, regardless of the route of administration.

Administration, Rectal↗
PubMed1997

Pharmacokinetics of cisapride in horses after intravenous and rectal administration.

OBJECTIVES: To determine the i.v. pharmacokinetics of cisapride and measure systemic absorption after rectal administration. ANIMALS: 5 healthy adult mares (380 to 610 kg). PROCEDURE: Cisapride was administered, i.v., at a dosage of 0.1 mg/kg of body weight. In the same horses, after a 1-week washout period, cisapride was administered rectally at a dosage of 1 mg/kg by mixing crushed tablets with propylene glycol and administering the mixture into the rectum. After each drug administration, a series of blood samples were collected. Plasma was obtained and analyzed by high-performance liquid chromatography to determine cisapride concentration profiles after each drug administration. RESULTS: After i.v. administration, peak plasma concentration was 221.4 ng/ml and harmonic mean half-life was 1.9 hours. Rectal absorption of cisapride was negligible. Cisapride was detected in plasma from only 3 of 5 horses for which mean systemic availability was 1.23%. Mean maximal plasma concentration after rectal administration of cisapride was 13.5 ng/ml. CONCLUSION AND CLINICAL RELEVANCE: After i.v. administration of cisapride, plasma concentration is high for approximately 2 hours. Cisapride mixed with propylene glycol and administered rectally at a dosage of 1 mg/kg is poorly and incompletely absorbed. Thus, cisapride is not clinically useful for rectal administration in horses.

Absorption↗
PubMed1999

Pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration in healthy subjects.

Clomethiazole, a sedative-hypnotic and anticonvulsant drug, has been successfully administered orally and intravenously, but in cases where either of these methods presents complications, rectal administration may represent a practical alternative. We sought to compare the single-dose pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration. Ten healthy adult volunteers were given 600 mg clomethiazole edisylate (corresponding to 390 mg clomethiazole base) in 2 capsules as a single oral or rectal dose in a double-masked, double-dummy, crossover fashion. Serum concentrations were measured up to 10 hours after administration using a specific high-performance liquid chromatography method. Computerized reaction-time measurement and visual analogue scales (VAS) were used to assess drug effects. Peak serum concentrations were significantly higher after oral administration (mean +/- SEM, oral 1.76 +/- 0.47 microg/mL vs rectal 0.48 +/- 0.14 microg/mL; P = 0.03) and appeared earlier (55 +/- 12 vs 89 +/- 11 min; P = 0.04). Area under the concentration-time curve values were similar after administration by both routes (oral 116 +/- 20.6 vs rectal 105 +/- 36.0 microg x min/mL), with a relative rectal bioavailability of 90% compared with oral administration. The objective pharmacodynamic effects on reaction time (increase of 104 +/- 26 vs 66 +/- 22 ms, oral vs rectal) and working speed (decrease of 132 +/- 38 vs 97 +/- 32 ms, oral vs rectal) were not significantly different. Subjective pharmacodynamic effects, as measured on the VAS, were comparable with both routes of administration. Clomethiazole was well tolerated, with a similar adverse effect profile for both routes of administration. The effects of rectal dosing of clomethiazole were similar to those of oral dosing but appeared to occur later. Our results suggest that rectal administration of a single 600-mg clomethiazole edisylate dose bears no safety risk. Therefore, rectal administration could be considered when neither oral nor parenteral administration is possible and a later onset of effect is not critical.

Administration, Oral↗
PubMed1988

Pharmacokinetics of ketamine HCl and metabolite I in the cat: a comparison of i.v., i.m., and rectal administration.

Ketamine HCl [2-(o-chlorophenyl)-2-(methylamino) cyclohexanone HCl] concentrations in whole blood were used to study the pharmacokinetics of i.v., i.m., and rectal administrations, at a dose of 25 mg/kg, in normal domestic cats. Absorption was rapid with both the i.m. and rectal routes. Systemic availability was 51% (SEM 10) for the i.m. dose and 43.5% (SEM 6.1) for the rectal dose. The first-pass effect had a minimal influence on the metabolism of ketamine HCl administered rectally. The elimination rate constant (beta) of the drug was statistically similar in the i.v., i.m., and rectal groups, at a 95% level of significance (P less than 0.05). At the dosage rates studied, ketamine HCl produced an anesthetic effect in the cat following i.v., i.m. and rectal administration.

Administration, Rectal↗