Biomedical subjects

G B Ritschel

Publications and source records attributed to G B Ritschel.

7 recordsLinked to original sources

PubMed1990

Improvement of peroral absorption of cyclosporine A by microemulsions.

The rat was found to be a suitable model for pharmacokinetic and bioavailability studies of cyclosporine A (CsA). All pharmacokinetic parameters studied were in the same order of magnitude as those found in man. Two peroral formulations in the form of microemulsions were compared with a commercially available P.O. solution (to be diluted for administration) and a solution for intravenous administration. Of the two microemulsions, one resulted in an extent of absolute and relative bioavailability significantly higher than that of the available P.O. solution. Biliary recycling was observed upon all routes of administration. If uncorrected for biliary recycling, both absolute and relative bioavailability are overestimated.

Administration, Oral↗

PubMed1989

Buccal absorption of insulin in the dog.

Insulin was buccally administered to beagle dogs in the form of a solution using a specially designed buccal cell, or in the form of films (buccal flats). 0.5 ml solutions of different pH (3, 4, 5, 6, 7.5) or of pH 7.5 in combination with sorption promoters (sodium taurocholate, dextran sulfate, linoleic acid, TranscutolR, LabrafilR M 1944 CS, urea and AzoneR) were administered for 0.5 h to anesthetized dogs. Buccal flats 1 X 2 cm in size. All dosage forms contained 10 IU of human insulin. The control solution (normal saline) and the solution of pH 5 resulted in the least pharmacologic availability, P.A. (ratio of area under % glucose reduction X time curve buccally to I.V.). Values of 0.9 % and 1.8%, respectively, were calculated. The insulin solution of pH 7.5 gave the highest P.A. The addition of sorption promoters to the pH 7.5 solution did not further increase the P.A. The combination of pH 7.5 - LabrafilR - AzoneR showed the least SD for the P.A., i.e. 18.3% +/- 4.7. The highest reduction in glucose concentration was found after administration of the taurocholate-linoleic acid combination Cmax = 57.2% +/- 6.3. The buccal flats reached a Cmax of about 16% +/- (SD) and a P.A of about 15% +/- (SD).

Absorption↗

PubMed1989

Study on the peroral absorption of the endekapeptide cyclosporine A.

The beagle dog was found to be a suitable model for pharmacokinetic and bioavailability studies of cyclosporine A (CsA). All pharmacokinetic parameters studied were in the same order of magnitude as those found in man. Three CsA peroral formulations in the form of capsules were compared with a commercially available P.O. solution (to be diluted for administration) and a solution for intravenous administration. Of the three experimental capsule formulations, one based on a microemulsion resulted in an extent of absolute and relative bioavailability not different from that of the available P.O. solution. The advantage, however, is that it is a capsule preparation, ready to swallow, and does not need any manipulation by the patient to dilute the solution. The other two capsule preparations, based on a Gelucire gel with sorption promoters and a microemulsion containing Azone, resulted in a lesser bioavailability than the solution.

Administration, Oral↗

PubMed1988

Insulin drug delivery systems: rectal gels.

In continuation of a previous study on insulin gels administered deep rectally by means of an applicator, 16 further rectal formulations were evaluated, using the nondiabetic White New Zealand rabbit as animal model. The highest pharmacologic availability, P.A., defined as the ratio of the areas under the % glucose reduction-time curves rectally versus I.V., corrected for dose size and body weight, in the previous experiments was about 29%. In the present study the highest mean P.A. was 42% and 31%, both obtained with Gelucire bases (50/22 and 44/14), pH 8 buffer solution and sodium deoxycholate, using Cab-O-Sil as stiffening agent. Simple gels prepared from gelatine and polyethylene glycol, or Veegum, resulted in mean P.A. of about 23 and 24%, respectively. Addition of Gelucire or sodium deoxycholate did not result in a further increase of P.A. of the latter two gels.

Administration, Rectal↗

PubMed1988

Rectal delivery system for insulin.

The purpose of this investigation was to first screen for potential effectiveness several rectal gels as insulin delivery systems and to select one promising dosage form as candidate for further evaluation in rabbits and man. Criteria for effectiveness were the "pharmacologic availability", determined as the ratio between the total area under the percent glucose reduction versus time curves upon rectal administration and the standard (I.V. for rabbits and S.C. for man), the maximum reduction in glucose blood concentration, the time to reach the maximum and the mean residence time of glucose reduction. The rectal gels consisted of emulsion systems prepared from pH 8 buffer solution containing insulin, an oleaginous phase, a surface active agent (bile salts, Myrj or Brij), and a viscosity increasing agent. The finally selected rectal gel was tested in rabbits both in a parallel and a crossover design in nondiabetic and diabetic animals. The selected rectal gel in nondiabetic and diabetic rabbits resulted in a pharmacologic availability of about 25%. By addition of Azone the pharmacologic availability was further increased, although not significantly (small n). In nondiabetic man the pharmacologic availability was about 32%, whereas the bioavailability (measured from plasma insulin) was only about 11%. Drugs undergoing hepatic first-pass metabolism and for which the liver is the biophase, should show increased pharmacologic availability with decreased bioavailability (if the latter one is due to first-pass effect).

Administration, Rectal↗

PubMed1984

Therapeutic concentration of coumarin as antipyretic.

Using a model previously described the antipyretic effect of coumarin (C) was studied with administration by constant rate infusion. A parallel design was used in the present study with 6 rabbits each in the following groups: (1) control, (2) with C 0.06 mcg/ml as desired steady state concentration for I.V. infusion after a loading dose, (3) endotoxin 0.125 mg/kg I.V. push, and (4) C I.V. Infusion with 0.06 mcg/ml steady state concentration after a loading dose plus endotoxin 0.125 mg/kg I.V. push. C in presence of endotoxin challenge reduces the elevated temperature significantly throughout the entire time of the experiment. Whereas C alone does not cause lowering of normal body temperature, in febrile condition the elevated temperature is reduced to below baseline levels. Based on these and previous findings it is hypothesized that C exhibits an aspirin-like action.

Animals↗

PubMed1984

Rectal administration of insulin.

According to recent statistics for the time span 1951-1970, the mortality ratio of diabetics to non-diabetics was 335% (46). For those diabetics who were younger than 15 years when entering the study, the mortality ratio was 1127%, with a mean life expectancy of another 32 years, as compared to 59 years for non-diabetics. Among the major causes of disablement and early death are ischemic heart disease, retinopathy, nephropathy, peripheral vascular disease and neuropathy. In spite of newer, more potent and highly purified insulins, development of human insulin, change of once-daily injection to twice-daily insulin therapy (47), and the introduction of portable insulin infusion pumps, diabetes is still a high-risk disease, far from being controlled. Considering that the present mode of insulin administration is by the subcutaneous route by which the insulin is presented to the body in a nonphysiological manner, because the insulin is peripherally administered to the systemic circulation instead of portally, new therapeutic ways for insulin administration are worth study. During the past years, considerable interest has arisen in the rectal route of administration. Based on a physiological-kinetic model presented in this paper, utilization of the first-pass effect inherent to the rectal anatomy offers a physiological insulin input via the rectal route of administration. A review on the present state of rectal insulin administration is given, and experimental data from our laboratories are presented. The usefulness of sorption promoters on rectal insulin absorption is discussed. The "effectiveness" of rectal insulin preparations is suggested to be evaluated by four criteria: the pharmacological availability via the area under the % glucose reduction-time profile, the maximum glucose concentration reduction, Cmax, the time to reach the maximum reduction, tmax, and the mean residence time for glucose reduction, MRT.

Animals↗