Investigation of physical and hypoglycaemic properties of rectal suppositories with chosen insulin

Rectal suppositories with insulin Humulin M3 (30/70) were prepared. Witepsol H15 and a polyoxyethyleneglycol mixture, composed of PEG 400, PEG 1000 and PEG 6000, were used as bases. Tween 60 and sodium salicylate were used as auxiliary substances. Hypoglycaemic properties of the prepared suppositories were tested on rabbits. The obtained results were compared with the data acquired after intravenous administration of insulin and subcutaneous injection of insulin.     

Absorption of phenytoin from rectal suppositories formulated with a polyethylene glycol base

STUDY OBJECTIVE: To compare phenytoin pharmacokinetics following administration of an oral suspension and a rectal suppository formulated with a polyethylene glycol base. DESIGN: Unblinded, single-dose, randomized, crossover trial. SETTING: University-affiliated pharmacokinetics and biopharmaceutics laboratory. SUBJECTS: Six healthy subjects. INTERVENTION: Subjects were given a single 200-mg dose of phenytoin as an oral suspension and a rectal suppository separated by a 1-week washout. MEASUREMENTS AND MAIN RESULTS: Blood for plasma phenytoin concentrations was obtained at baseline and 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hours after administration. Plasma was analyzed by high-performance liquid chromatography (coefficient of variation < 6%) for total phenytoin concentration. Phenytoin maximum concentration (Cmax), time to Cmax (Tmax), time to first measurable concentration (Tlag), and area under the curve from time zero to time of last measurable concentration (AUClast) were estimated for oral and rectal administration by WinNonlin (v 1.1) and compared using Wilcoxon's signed rank test (p<0.05 for statistical significance). Two subjects did not have detectable plasma phenytoin concentrations after rectal administration. For the other four subjects, median rectal Cmax was significantly lower than oral Cmax (0.4 vs 1.9 microg/ml, p=0.028), median rectal Tmax did not differ from oral Tmax (11.9 vs 8.0 hrs, p=0.465), and median rectal AUClast, although highly variable, was significantly lower than oral AUClast (5.4 vs 36.2 microg x hr/ml, p=0.046). No Tlag was seen after oral administration, but with rectal administration the median Tlag was 2 hours. The estimated relative bioavailability of rectal phenytoin suppositories based on AUC0-24 was 4.7%, with individual values ranging from 0-58.3%. CONCLUSION: It appears that absorption of phenytoin from polyethylene glycol rectal suppositories in healthy subjects is highly variable and unpredictable. Thus this formulation is not recommended.     

The bioavailability of seven commercially available rectal aminophylline suppositories

The bioavailability and thein vitro parameters of seven aminophylline 360 mg suppositories were compared with an oral hydroalcoholic solution of aminophylline as reference, using cross-over designs in groups of four subjects in single dose experiments. Plasma concentrations were followed for eight hours after drug administration. Four products gave extents of bioavailability of less than 80% of the reference solution. A dissolution test gave results which did not correlate well with the bioavailability results. It was concluded that no satisfactory plasma levels can be reached with the examined dose of aminophylline after single administration of one suppository.Calculation of the steady-state concentration was performed as well as a graphic simulation of the plasma concentration-time curves, after repeated administration; it was demonstrated that with most of the suppositories no sufficiently high level could be obtained after three doses per day.In honour of ProfessorHuizinga on the occasion of his retirement.     

Release and rectal absorption of ethosuximide from suppositories in rabbits

Ethosuximide was formulated in different suppository bases. In vitro release experiment demonstrated more rapid and higher release of the drug from water soluble polyethylene glycol (PEG) bases than from Witepsol fatty bases. Rectal administration in PEG 400:4000 and 400:6000 to rabbits gave high plasma levels where Cmax was 45.66 and 42.66 micrograms.ml-1, respectively; while, in the presence of Witepsol E76 and W35 it was 34.00 and 28.33 micrograms.ml-1, respectively. The systemic availability was 89.39%, 82.72%, 58.80% and 47.45% when the bases were PEG 400:4000, PEG 400:6000, Witepsol E76 and Witepsol W35, respectively.     

复方吲哚美辛栓直肠给药对产科手术切口的止痛作用

目的：观察复方吲哚美辛栓治疗分娩术后切口痛的疗效。方法：对４５例会阴切开术和４０例剖宫产的分娩产妇，前者在产后次日直肠给复方吲哚美辛栓１枚（每枚含吲哚美辛７０ｍｇ和沙丁胺醇１．２ｍｇ），ｑｄ×３ｄ；后者在术日麻醉效果消失后给药，用法同前，共４次。对照组６７例，其中３５例是会阴切开术，在分娩次日给安乃近１片（０．５ｇ／片）ｐｏ，ｑｄ×３ｄ，３２例剖宫产，在术日麻醉效果消失后给丁丙诺啡１支（１００ｍｇ／支）ｉｍ，ｑｄ×３ｄ。结果：止痛作用达优、良的有效率，复方吲哚美辛组各为１００％和９５％，对照组各为５４％和４１％。２相关组疗效相比Ｐ皆＜０．０１。结论：复方吲哚美辛栓对产科术后镇痛的效果良好。     

Pharmacokinetics of theophylline in young children with asthma: Comparison of rectal enema and suppositories

Summary Six children, aged 2 months – 4 years, received theophylline 5–6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t_1/2 β) was 3.75 h, i. e., shorter than in adults, but there was a considerable interindividual variation (1.8–7.0 h, in one patient 13.3 h). Thirteen children (2 months – 4 years) received theophylline suppositories in a dose of 3.8–5.0 mg/kg, and ten (6 months – 4 years) in a dose of 8.4–14.5 mg/kg. Absorption was slow (mean half-time 43 min), incomplete and variable (biological availability 8–100%, mean 80%). Only four of the patients given the higher dose and none given the lower dose reached a therapeutic serum concentration (10–20 μg/ml). Nine children (6 months – 4 years) received rectal enemas of theophylline 4.1–9.2 mg/kg. Absorbtion was rapid (mean half-time 5.5 min) and biological availability averaged 100%. Six patients reached a serum concentration within the therapeutic range. Using the mean values of the calculated pharmacokinetic parameters, rectal enemas providing a dose of theophylline of 6–8 mg/kg t. i. d. were computed to give serum concentrations between 8–20 μg/ml, without producing too high a level during the absorption phase.     

Fundamental and clinical studies of ceftizoxime rectal suppositories in the field of pediatrics

This paper deals with fundamental and clinical results, in the field of pediatrics, of the newly developed rectal suppository (CZX-S) of a cephem antibiotic ceftizoxime (CZX). CZX-S was well absorbed in children. The mean peak serum concentrations of CZX in the 125 mg-administered group (average: 9.9 mg/kg) and the 250 mg-administered group (average: 13.4 mg/kg) were 5.10-7.71 micrograms/ml at 15-30 minutes after dosing. Serum concentrations of CZX were measurable level in almost all the children at 6 hours after administration with the half-lives were 1.34-1.55 hours. The 6-hour urinary excretion rate accounted for 16.5-22.0%. CZX-S was administered to 30 children with acute upper or lower respiratory tract infections about 20-60 mg/kg/day in 3-4 divided portions. CZX-S provided favorable therapeutic-effect in most of the children 3-5 days after administration. The effectiveness rate was 93%. The causative organisms of H. influenzae (3 cases) and S. aureus (4 cases) isolated clinically from pharyngeal mucous and sputum were eradicated after administration of CZX-S. Anal pain and diarrhea experienced in 5 of the 30 children and CZX-S was withdrawn in 4 (of the 5) children, but exhibited satisfactory therapeutic-effect in 2 of the 4 cases up to withdrawal of the drug. An increase in GOT and GPT was observed in 3 cases. The values returned to the normal range in 1 case after the treatment with CZX-S. The test was not reexamined in the other 2 cases. The present clinical result suggests the usefulness of CZX-S substituted for oral and injectable forms in the treatment of various pediatric infections caused by organisms sensitive to CZX.