Search PubMed⌕ Search

Biomedical subjects

J Bircher

Publications and source records attributed to J Bircher.

At least 109 records · Page 6Linked to original sources
PubMed1978

Rate of drug metabolism in man measured by 14CO2-breath analysis.

Exhalation of 14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of 14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of 14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of 14C-demethylation breath tests. In particular, they are consistent with the hypothesis that 14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.

Adult↗
PubMed1978

[Blood cholinesterase and hepatic function: a comparison with BSP and galactose elimination as well as serum albumin concentration].

Although quantitative tests of some hepatic functions have been well established, the determination of serum cholinesterase activity continues to be commonly used in their stead. A critical comparison of the serum cholinesterase activity with these quantitative tests, however, is still lacking. Serum cholinesterase activity was therefore simultaneously compared with galactose elimination capacity (GEC), initial BSP-disappearance rate (BSP-ki), and serum albumin levels in 19 healthy control subjects and 46 patients with various chronic liver diseases. Serum cholinesterase activity was less discriminating between controls and patients than BSP-ki. It appears poorly suited, therefore, as a screening test for mild liver disease. Rank correlations between serum cholinesterase activity and GEC, BSP-ki, and serum albumin were statistically higher significant (r = 0.65, r = 0.74, and r = 0.80 respectively). On a statistical basis, serum cholinesterase activity may, therefore, be regarded as an index of the functional reserve of the liver. Evaluation of individual cases, however, revealed some clinically relevant discrepancies. It is concluded, therefore, that for accurate follow-up studies measurements of serum cholinesterase activity may be insufficient substitutes for the quantitative tests.

Adult↗
PubMed1978

[Indications and contraindications of liver biopsy].

In each individual case the indication for liver biopsy depends on assessment of the risks relative to the potential benefits of the procedure. Besides hepatological risk factors, hemostasis and overall health problems must be considered. The benefit of liver biopsy is dependent on recognition of the pathognomonic lesion within the tissue sample obtained. Size and distribution of the different histological features and the size of the biopsy cylinder are, therefore, important determinants for the success of the examination. Whether or not a histological diagnosis may be useful for optimal management of a patient can best be judged if the clinical question has been well defined before the biopsy is performed.

Biopsy↗
PubMed1978

Hepatic metabolism of aminopyrine in patients with chronic renal failure.

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0.62 +/- SD 0.24 h-1) were significantly higher than those found in normal subjects (0.30 +/- 0.07 h-1, P less than 0.002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0.40 +/- 0.04 h-1) than in control subjects (0.22 +/- 0.03 h-1, P less than 0.01) and in other patients with chronic renal failure (0.24 +/- 0.04 h-1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.

Adult↗
PubMed1978

Polymorphic acetylation and aminopyrine demethylation in Gilbert's syndrome.

Polymorphic acetylation was investigated in twenty-seven patients with Gilbert's syndrome using the sulphadimidine test. Whereas the finding of 51% slow acetylators in seventy-eight control persons agreed well with the expected frequency in a continental European population, the prevalence of slow acetylators in Gilbert's syndrome was increased to 78% (P less than 0.03, Woolf's G-test). After oral administration of 14C-aminopyrine there was no significant difference between seventeen patients with Gilbert's syndrome and twenty-seven normal controls in total plasma clearance of aminopyrine (280 +/- SD 100 and 270 +/- 60 ml/min) and in the disappearance curve of 14CO2 in breath (0.23 +/- 0.04 and 0.22 +/- 0.03 h-1, respectively). Thus, whereas aminopyrine metabolism appears unaffected in the examined patients, the data documents a new association between slow acetylator status and Gilbert's syndrome.

Acetylation↗
PubMed1978

[Hepatic hemodynamics and function (author's transl)].

Methods to quantitatively assess all the hemodynamic alterations which occur in cirrhosis of the liver unfortunately are not as yet available. Within this context, transhepatic catheterization of portal vein branches represents a real progress. A better understanding of the pathophysiology of the BSP plasma disappearance curve has revealed that the second exponential component (k2) is particularly useful for the early diagnosis of cholestasis.

Catheterization↗
PubMed1977

Dose dependence of the 14C-aminopyrine breath test. Intrasubject comparison of tracer and pharmacological doses.

Although the aminopyrine breath test has received much attention, the question has not yet been settled whether pharmacological or tracer doses of the drug should be used. Nine volunteers were given 14C-aminopyrine 9 mg/kg or a tracer amount, in a randomized sequence and according to a crossover design. The specific activity of 14CO2 in breath was significantly different only during the first hour. Up to the 8th hour the disappearance of 14CO2 from breath was smaller after the pharmacological (28.5 +/- SD 5.4%/h) than after the tracer dose (36.2 +/- 10.6%/h; p less than 0.05). The over-all disappearance of 14C-atoms from the subjects was significantly slower after the higher dose. In view of the smaller radiation exposure and the decreased risk of agranulocytosis, the use of a tracer dose appears preferable.

Aminopyrine↗
PubMed1977

[Does cholestyramine impair the bioavailability of prednisolone?].

Measurements of plasma prednisolone concentrations in two patients who received orally 37.5 and 75 mg of the drug respectively showed no differences when 8 g of cholestyramine was given with the corticosteroid. Thus, no influence of cholestyramine on the bioavailability of orally administered prednisolone could be demonstrated.

Biological Availability↗
PubMed1977

[The aminopyrine respiratory test under the acute effect of ethanol. Evaluation of a new method for the measurement of microsomal functions of the liver].

Microsomal demethylation, a partial function of the liver, can be estimated by the aminopyrine breath test. Both the determination of specific activity and the disappearance rate constant for 14CO2 in breath demand the assumption of rapid formaldehyde oxidation to CO2. Conversely, the disappearance of aminopyrine from plasma reflects microsomal aminopyrine metabolism only. Ethanol is known to affect both microsomal demethylation and formaldehyde metabolism. If in the presence of ethanol the latter process should become rate-limiting, a discrepancy between the data obtained in breath and in plasma could be expected. In order to investigate this possibility 10 fasting healthy male volunteers received 9 mg/kg (dimethylamine-14C)-aminopyrine (2 muCi) orally and, 3 hs later, 0.7 g/kg ethanol. Immediately following ethanol the specific activity of 14CO2 in breath decreased by 25% (p less than 0.005) and the disappearance of 14CO2 from breath was 31% lower than in 17 matched controls (p less than 0.005). The aminopyrine plasma disappearance rate, determined by GLC, decreased by 30% after ethanol (p less than 0.05). Since the decrease in aminopyrine plasma disappearance rate seems to account for the proportional decreases obtained by breath analysis, it is concluded that the aminopyrine breath test expresses the rate of microsomal demethylation even during altered formaldehyde metabolism, e.g. in acute ethanol intoxication.

Aminopyrine↗
PubMed1977

The influence of prednisolone on hepatic function in normal subjects. Effects on galactose elimination capacity, sulfobromophthalein transport maximum and storage capacity, and D-glucaric acid output.

In view of the importance of liver tests in the follow-up of patients under treatment with corticosteroid hormones, 20 mg of prednisolone were given by mouth to normal volunteers for 4 days and hepatic function was assessed before and during treatment. Despite significant falls in plasma cortisol and serum bilirubin concentrations, the galactose elimination capacity, the BSP tests, and the urinary D-glucaric acid output remained essentially unchanged. Consequently no pharmacological effect of this corticosteroid hormone on the examined tests could be detected.

Administration, Oral↗
PubMed1977

The defect of uric acid metabolism in Eck-fistula rats.

Because of the discovery of uric acid urolithiasis in rats after end-to-side portacaval anastomosis (PCA), uric acid metabolism was studied in these animals and in appropriate controls. Hyperuricemia and hyperuricosuria were observed in all experimental rats. The fraction of purine catabolites excreted in the urine as uric acid increased from an average of 4.8% to 15.3%. If 14C-uric specifically labeled at position 6 (6-14C-ua) was infused intravenously and the exhalation of 14CO2 was used to calculate a hepatic uric acid clearance, it decreased from 2.14 to 0.97 ml/min/100 gm despite a normal content of hepatic uricase activity as measured in liver homogenates. The fraction of the filtered amount of uric acid excreted in the urine increased from an average of 11% to 30%. Increased supersaturation of the urine with uric acid after PCA may be expected to contribute to the formation of uric acid urolithiasis. This investigation defines a hepatic and renal functional defect in uric acid metabolism which occurs as a result of the PCA.

Allantoin↗
PubMed1977

Stereoselective metabolism, pharmacokinetics and biliary elimination of phenylethylhydantoin (Nirvanol) in the dog.

The influence of stereoisomerism on pharmacokinetics and rates of hepatic drug metabolism was investigated in four dogs using the enantiomers of phenylethylhydantoin (PEH) as model substances. After single i.v. administration of 98 micromoles of the pure enantiomers per kg b.wt., concentrations were measured by gas-liquid chromatography. The l-form exhibited a longer plasma half-life (23.3 +/- S.E. 1.0 hour) than the d-form (16.3 +/- 1.0 hour, P less than .005). Volumes of distribution and renal clearances were practically identical. The differences in plasma half-lives of PEH were explained by stereoselectivity of hepatic hydroxylation: an approximately 10-fold differences was found in urinary excretion of their major metabolities, d- and l-hydroxyphenylethylhydantoin (HPEH). Furthermore, in bile 7.3 +/- 1.6 mumol of of d-HPEH were eliminated within the first 6 hours, whereas l-HPEH could not be detected. The preference in biliary output of d- compared with l-PEH is consistent with the idea that both hepatic uptake and microsomal hydroxylation of PEH contribute to the high degree of stereoselectivity. In view of similar extrahepatic, but different metabolic behavior of these enantiomers, they represent an interesting research tool for in vivo studies of drug metabolism: in otherwise identical conditions, two different rates of PEH hydroxylation may be studied.

Animals↗