Biomedical subjects
Publications and source records attributed to A Windorfer.
In numerous therapeutic regimens for infants it often happens that more than one drug is given. Most doctors however, do not know sufficiently if and to which extend an interaction between the different substances takes place in the human organism. Phenytoin in combination with other drugs (anticonvulsives, antibiotics etc.) demonstrates the many different mechanisms of interaction.
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A comparative pharmacokinetic study was performed for three different nitroglycerin application forms. Serum concentrations were determined in six healthy male volunteers aged from 25 to 29 years. The serum concentrations of nitroglycerin after application of nitroglycerin ointment (Neos-nitro-ointment), of a sustained-release capsule and a sublingual capsule demonstrated that the ointment shows a similar absorption rate (Kr = 0.957 h-1) as the sustained-release capsule (Kr = 1.244 h-1) and furthermore results in a twice as high serum concentration when given in a 30.4 mg nitroglycerin dose as compared to one sustained-release capsule. Since the elimination rate of nitroglycerin was determined similar in all three application forms with a half-life of t1/2 approximately equal to 5 min it can be stated that the duration of effect after the application of ointment is longer than that of the sustained-release form based on the higher serum concentration.
The bioavailability, the absorption and elimination rate (biological half-life) as well as the volume of distribution for different routes of application were tested for the myotonolytic N-(hydroxy-2-ethyl)-cinnamide (LCB-29). 60 mg were administered i.v., 400 mg p.o. and 400 mg or 7 X 200 mg as ointment. For the i.v. and oral application the serum levels as well as the urine levels were determined. The amount of LCB-20 which may have been present in the urine after the ointment application was below the limit of detection. Serum concentrations were determined 10 times within 24 h after each application. Based on these values an absolute bioavailabiltiy for the LCB-29-ointment could be estimated at 1% in an application on 200 cm2 skin. This proved that the absorption of LCN-29 as ointment is very low compared to that in the oral application (absolute bioavailability 30%). The half-life was determined to be quite similar for all 3 routes of application: approximately 1 h. The absorption rate decreased by the factor 1.7 when LCB-29 was administered cutaneously instead of orally.
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In a pharmacokinetic study with healthy test persons we compared the forte-tablet form of cotrimoxazol produced by 4 different manufacturers. We were able to show that 3 of the tested products (2 well known standard products I and II as well as a new comparative product) achieved nearly equal high serum concentrations of sulfamethoxazole and trimethoprim. The serum concentrations of a fourth product, a generic product, were lower for sulfamethoxazole and trimethoprim. As the difference is of no statistical significance and the serum concentrations of the last product are within the therapeutic range this product is also qualified for therapeutic use. When the dose is given after a standard breakfast the serum values of sulfamethoxazole were slightly higher than if given on an empty stomach. However, the serum values of trimethoprim given on an empty stomach were higher.
In 1977 in Bavaria, 7,659 cases (incidents) of tuberculosis were reported. 797 of these cases were children under 15 and 636 were youths between 15 and 20 years of age, that is 1,433 together. The first rise in cases takes place in the age bracket up to 5 years, the second, far greater, between 15 and 25. At the end of 1977 statistics showed the existence (prevalence) of 14,642 tuberculars. Of these, 1,128 were children under 15 and 858 youths between 15 and 20. Administrative districts with the most cases were Lower Bavaria (Niederbayern), Upper Palatinate (Oberpfalz), Upper Franconia (Oberfranken), and Middle Franconia (Mittelfranken). In local epidemics 190 youths and children became ill, infected in a dance hall, a discotheque, and a factory, as well as by a kindergarten teacher. Under these unfavorable circumstances a BCG vaccination is imperative. The Bavarian Home Ministry "publicly recommends" the BCG vaccination for infants as well as for all tuberculin negatives who live with people who have tuberculosis or who are otherwise endangered by tuberculosis, However, under the circumstances described, all children and young adults are still endangered by tuberculosis.
The advances of civilization are more and more endangering the development of the child. The most important problems are traffic accidents, the decay of the family, the falling birth-rate and the increasing abuse of drugs and alcohol as well as suicide in early years of life. The family and the child must be respected in the future to improve the situation. Adults have to accept the age specific problems of the child.
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In a retrospective study of 2618 pregnant women we examined the influence of diazepam monotherapy as well as the combination of diazepam and fenoterol on the bilirubin concentrations and Apgar scores of the newborn children. In the diazepam-treated group 17-27% of the newborns showed Apgar scores of 6 or less. In the group treated with diazepam and fenoterol, 66-68% of the newborn had Apgar scores of 6 or less. The effect of diazepam on the bilirubin levels appears to depend on the dose and duration of the diazepam treatment: low, short term diazepam doses cause a slight bilirubin increase, while higher diazepam doses cause a reduction of the bilirubin levels. Following the combination therapy of diazepam and fenoterol a significant number of the infants developed neonatal jaundice. Due to the fact that following the combination therapy the diazepam concentration of the newborns were higher than following the monotherapy, we ascribe the greater frequency of the low Apgar values and also possibly the larger bilirubin increase to the higher diazepam concentration caused by fenoterol.
In a single-dose study three different dosage forms of nitrofurantoin tablets are compared in order to attain a longer duration of efficacy by means of sustained-release dosage forms. In particular, bioavailability and the rate constants are estimated and show for one dosage form significant advantages. The measured serum and urine concentration levels are evaluated with a two-compartment model of first order which assumed the sustained release of the drug in an exponential manner.
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