[Follow-up studies of patients with negative TRH test and normal thyroid hormone levels]. / Verlaufsbeobachtungen bei Patienten mit negativem TRH-Test und normalen Schilddrüsenhormonspiegeln.

The aim of the study was to assess the clinical significance of the association of a negative TRH-test with normal thyroid hormone levels. Therefore, we repeated the investigation in 63 patients one year after the first examination. In 6 patients (10%) hyperthyroidism had developed. Euthyroid autonomy was diagnosed in 11 patients (17%). A prolonged normalisation period of the pituitary-thyroid regulation after having discontinued the thyroid hormone drugs was found in 7 patients (11%). In 40% of the patients the TRH-test remained negative and in 22% of the patients the TSH-response became positive without any known reason. The findings show that a negative TRH-test and normal thyroid hormone levels do not necessarily imply subclinical hyperthyroidism.

[The effect of intrahepatic cholestasis in pregnancy on various forms of cytochrome P-450-dependent biotransformation reactions]. / Der Einfluss der intrahepatischen Schwangerschaftscholestase auf verschiedene Cytochrom P-450-abhängige Biotransformations-reaktionen.

The elimination of caffeine from plasma and the excretion of the main metabolites of metamizol (noramidopyrinemethanesulphonate sodium) into the urine were determined in healthy pregnant women (weeks 30-38 of pregnancy) and in patients with intrahepatic cholestasis in pregnancy (weeks 28-39 of pregnancy). From the elimination velocity of these model substances conclusions concerning the activity of 3-methylcholanthrene (caffeine elimination) and phenobarbital inducible isoenzymes (metamizol elimination) of cytochrome P-450 are drawn. Patients with intrahepatic cholestasis in pregnancy (t1/2 = 15.8 +/- 1.8 h) eliminate caffeine more slowly than healthy pregnant women (t1/2 = 11.0 +/- 0.8 h) at this stage of pregnancy. The excretion of the metabolites of metamizol is only in tendency diminished in patients with intrahepatic cholestasis. The influence of the intrahepatic cholestasis on the cytochrome P-450 isoenzymes investigated differs in degree.

Increase of 14C-leucine uptake following stimulation of renal tubular transport processes.

Following treatment with cyclopenthiazide, triiodothyronine or dexamethasone the renal excretion of p-aminohippurate (PAH) as well as the accumulation of PAH in renal cortical slices from adult rats and from rats with immature kidney function are increased. There are differences with respect to the age of the rats as well as in dependence on the substance used for treatment. In 10- and 60-day-old rats the [14C]leucine uptake following such a stimulation of kidney function is increased, that means active tubular transport of amino acids can also be stimulated. Furthermore, the [14C]leucine content in the protein fraction of homogenized kidney tissue is increased, indicating a higher degree of incorporation of amino acids in kidney tissue following treatment with cyclopenthiazide, triiodothyronine or dexamethasone.

[Elimination of caffeine and metamizol in in vivo characterization of cytochrome P-450 dependent biotransformation reactions in aged humans]. / Die Elimination von Coffein und Metamizol zur in-vivo-Charakterisierung Cytochrom P-450-abhängiger Biotransformationsreaktionen beim alten Menschen.

Elimination of caffeine from plasma and excretion of main metabolites of metamizol (noramidopyrine methanesulphonate sodium) in urine were determined in young healthy (age 18-27 years) and in old aged volunteers (older than 65 years). From the elimination velocity of these model substances conclusions concerning the activity of 3-methylcholanthrene inducible (caffeine elimination) and of phenobarbital inducible (metamizol elimination) isoenzymes of cytochrome P-450 are drawn. Whereas in old age caffeine metabolism is unchanged, there is a strong delay in renal excretion of main metabolites of metamizol in old volunteers. It is concluded that different hepatic cytochrome P-450 isoenzymes are differentially influenced with increasing age in men.

[The influence of chronic renal insufficiency on the demethylating activities of various cytochrome P-450 subspecies in humans]. / Einfluss der chronischen Niereninsuffizienz auf durch verschiedene Cytochrom P-450-Subspezies katalysierte Demethylierungsaktivitäten beim Menschen.

Caffeine is mainly metabolized by 3-methylcholanthrene-inducible cytochrome P-450 (P-450MC) and metamizol (noramidopyrine methanesulfonate sodium) is mainly metabolized by phenobarbital-inducible cytochrome P-450 (P-450PB). That's why the half life of caffeine and the elimination of the main metabolites of metamizol were used as parameters in vivo characterizing both groups of the cytochrome P-450-complex. The influence of chronic renal insufficiency was investigated (8 patients in the stage of compensated retention, creatinine in serum 380-1280 mumol X l-1, and 6 hemodialyzed patients, here only metamizol elimination was established). Both the caffeine and the metamizol eliminations of patients with chronic renal insufficiency are not different from those of healthy volunteers. We concluded that the demethylation activity of the cytochrome P-450-complex is not distinctly influenced by chronic renal insufficiency.

[Determination of caffeine and metamizole elimination in pregnancy and after delivery as an in vivo method for characterization of various cytochrome p-450 dependent biotransformation reactions]. / Bestimmung der Elimination von Koffein und Metamizol in der Schwangerschaft und im Wochenbett als in vivo-Methode zur Charakterisierung verschiedener Zytochrom P-450-abhängiger Biotransformationsreaktionen.

The elimination of caffeine from plasma and the elimination of the main metabolites of metamizol in urine were measured in 20 pregnant women, 19 puerperants, and 10 young healthy female non-pregnant volunteers. It was found a significant prolongation of caffeine elimination in pregnancy (t 1/2 = 9.4 +/- 0.6 h) with a correlation between duration of pregnancy and elimination half-life of caffeine (v = 0.72). The amount of the main metabolites of metamizol eliminated 0-9 h after application of the drug decreased from 82.6 +/- 8.2 mg in nonpregnant volunteers to 45.6 +/- 5.7 mg in pregnant women. Whereas caffeine elimination is restored within the first week after delivery, the rate of metamizol elimination does not reach the value of the non-pregnant volunteers in this period.

[Determination of caffeine and metamizole elimination in men and women with and without hormonal contraceptives as an in vivo method for characterization of various cytochrome P-450 subspecies]. / Die Bestimmung der Coffein- und Metamizolelimination bei Männern und Frauen ohne sowie unter hormonalen Kontrazeptiva als in-vivo-Methode zur Charakterisierung verschiedener Cytochrom P-450 Subspezies.

Caffeine is mainly metabolized by 3-methylcholanthrene-inducible cytochrome P-450 (P-450MC) and noramidopyrine-methanesulfonate sodium (metamizol, Analgin) is mainly metabolized by phenobarbital-inducible cytochrome P-450 (P-450PB). We investigated the elimination of caffeine by the use of plasma concentration curves (HPLC) and the elimination of metamizol by spectrophotometric determination of the metabolites in urine in 10 healthy young males, in 10 healthy young females using no OL-steroids and in 10 healthy young females using OC-steroids. No influence of sex on the microsomal drug metabolism activity of these two drugs has been observed. There was a significantly decreased microsomal drug metabolism of both drugs in females under hormonal contraception. We conclude that OC-steroids decrease the demethylation activity of both P-450MC and P-450PB.