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K Bachmann

Publications and source records attributed to K Bachmann.

At least 163 records · Page 9Linked to original sources
PubMed1985

Phenytoin as a probe of drug metabolism. Predicting clearance with a salivary sample.

Phenytoin (PHT) was administered in single 300-mg doses to each of 12 healthy, male subjects. Serial blood samples and salivary samples were collected for the next 48 h, and concentrations of plasma total PHT, unbound plasma PHT (plasma ultrafiltrates), and salivary PHT (salivary ultrafiltrates) were measured by immunofluorescence polarization. The following parameters were estimated: CLint/F, CL'int/F, V/F, and total and unbound PHT plasma disappearance half-lives. Estimates of CL'int/F (CL'int/F) were calculated from single 48-hour salivary PHT measurements. Mean (+/- SD) values were 0.026 +/- 0.009 1 . h-1 . kg-1, 0.385 +/- 0.148 1 . h-1 . kg-1, 12.6 +/- 3.5 l/kg (referenced to unbound drug), 28.0 +/- 12.1 h, and 25.9 +/- 13.5 h, respectively. When V/F referenced to unbound PHT was set at 14 l/kg, CL'int/F estimates were good predictors of the actual CL'int/F values demonstrating a mean prediction error of -9.012 1.h-1.kg-1. These data demonstrate that under specified conditions, intrinsic unbound PHT clearance can be estimated from a single PHT measurement in saliva, thereby permitting PHT to be used safely and sampled simply and noninvasively as a probe of hepatic mixed function oxygenase activity in humans.

Adult↗
PubMed1985

Triiodothyronine (T3)-induced thermogenesis: altered T3-efficiency in tissues from fed, starved, and refed hypothyroid rats.

A microcalorimetric study of perifused tissue samples obtained from hypothyroid thyroidectomized rats killed 15 h after a single injection of T3 was conducted in order to observe at the tissue level, and in a constant environment, the T3-dependent thermogenesis induced in fed, starved, and refed states. When 9 micrograms T3/100 g BW had been administered to fed animals, tissue heat production rate (E) increased in liver, soleus muscle, and myocardium. In kidney cortex an increase in E was observed only after 90 micrograms T3. A dose-response study was performed with liver samples, in which both oxygen consumption and heat production rates were measured. Liver and soleus muscle were then further investigated. T3-dependent thermogenesis could not be demonstrated in tissues obtained from rats which had been starved for 3 days before receiving 9 micrograms T3/100 g BW. After a small carbohydrate intake corresponding to about 60 kJ/rat (refed state; 1 kJ congruent to 0.4 kcal) given over a 3-h period preceding the injection of T3, T3-dependent thermogenesis was again present. It is concluded that differences in T3 dependent thermogenesis similar to those previously observed in animals under different nutritional states continue to exist in vitro, when tissues are no longer exposed to differing levels of humoral factors.

Animals↗
PubMed1985

Variations of 3-methylhistidine in blood of dairy cows.

Blood plasma 3-methylhistidine, in comparison with other blood variables, has been measured in high-yielding dairy cows with relation to energy and protein supply. Circulating 3-methylhistidine markedly increased to 1 wk after calving, then continuously decreased to 5 wk postpartum to lower than during the last 2 wk of pregnancy. In experiments 36 d after calving, circulating 3-methylhistidine did not change during 24 h despite marked variations of food intake. Peak 3-methylhistidine immediately after parturition coincided with relatively low insulin, thyroxine, triiodothyronine, glucose, protein, and urea with elevated concentrations of nonesterified fatty acids and with greatest estimated energy and protein deficiencies. However, during the ensuing period to 12 wk of lactation, circulating 3-methylhistidine was not closely related to these measures nor to creatinine, beta-hydroxybutyrate, and milk production, but relationships to milk protein yield were close. The postparturient increase of 3-methylhistidine may have been a consequence of enhanced breakdown of skeletal muscle and uterine smooth muscle or another pool with a transiently enhanced turnover rate. Variations of plasma 3-methylhistidine were associated only in part with estimated negative energy and protein balances and corresponding endocrine and metabolic adaptations.

Animals↗
PubMed1985

Hepatitis B vaccine and antipyrine clearance.

The impact of hepatitis B vaccine on hepatic mixed function oxidase activity was studied using antipyrine as a probe. Fifteen health care workers who elected to take the vaccine due to occupational risk were the subjects. Each subject received all three vaccinations over a period of six months. Antipyrine (500 mg) was administered orally prior to the first vaccination, 1 week subsequent to each vaccination, and one month after the final vaccination, and antipyrine clearance, CL/F was estimated from concentrations of antipyrine in saliva collected 24 hr after each antipyrine dose. The mean (+/- SD) pre-vaccination CL/F was 3.65 (+/- 0.75) 1/hr. Post vaccination mean CL/F values deviated by no more than 8.8% and none of the post vaccination values were significantly different from the pre-vaccination mean. It is inappropriate to extrapolate findings concerning one antiviral vaccine and its putative effect on drug metabolism to other antiviral vaccines.

Adult↗
PubMed1984

Plasma levels of 3-methylhistidine after ingestion of the pure amino acid or of muscular proteins measured by radioimmunoassay.

A radioimmunoassay for plasma 3-methylhistidine (3MeHis) measurements has been developed. The assay has no significant crossreactivity with 18 other amino acids including histidine, carnosine, anserine, and creatinine. In normal subjects who have eaten no meat for 36 hours, plasma levels are constant over a 24-hour period (8.78 +/- 0.48 mumol/L, mean +/- SD). The use of 3MeHis for the assessment of intestinal protein absorption and its potential use as a marker of protein degradation were evaluated by studying its plasma kinetics. The absorption of the free 3MeHis is rapid and reaches a peak after 75 minutes. The peak is delayed after meat ingestion and reaches a maximum after 180 minutes. The ratio of the 75- to 180-minute 3MeHis levels was 1.40 +/- 0.06 for pure 3MeHis and 0.78 +/- 0.06 after meat ingestion (P less than 0.001). Peak height and area under the plasma concentration versus time curve were proportional to the dose received, indicating first order kinetics for 3 MeHis. It has a half-life of 12.2 hours, a metabolic clearance rate of 0.08 L/h and volume of distribution is 11.7 +/- 1.7 L as calculated from the serum values which were obtained up to 24 hours after oral 3MeHis administration. Its endogenous production can therefore be calculated to be 116 mumols per day in young subjects. Thus, the radioimmunoassay develops the potential of this amino acid as a marker of protein degradation and absorption for physiological investigations.

Adult↗
PubMed1984

Use of plasma unbound drug concentrations in adjusting phenytoin doses.

The application of a Bayesian feedback algorithm for phenytoin (PHT) dosing adjustments was modified empirically to take advantage of measurements of plasma unbound PHT concentrations in the estimation of Km values. Doses were calculated to achieve steady-state unbound PHT nadirs of 1.2 mg/L with an allowable range of 0.9-1.5 mg/L. The success of this approach was compared with that of a routine strategy encompassing the use of monitored total plasma PHT concentrations and no estimates of kinetic parameters. Allowing up to a double feedback of monitored values, the Bayesian approach was better than the routine procedure in predicting doses that led to PHT concentration within the targeted range (p less than 0.005). The approach to optimizing PHT dosing described herein offers the advantage of rapidly converging on near-optimal therapy for those patients who are already on PHT but whose seizures are not suitably controlled, and may be useful even for patients who exhibit abnormal PHT plasma protein binding, such as those who also must take valproic acid.

Adolescent↗
PubMed1984

The effect of erythromycin on the disposition kinetics of warfarin.

Erythromycin is generally regarded as innocuous in regard to adverse interactions with other drugs. Recently, however, its potentiation of theophylline and warfarin has been reported. The present investigation defined more specifically the kinetics of the interaction between erythromycin and warfarin. Warfarin kinetics were evaluated in 12 normal subjects who took a single 1 mg/kg dose of warfarin with and without erythromycin. Erythromycin (250 mg p.o.) every 6 h for 8 days decreased warfarin clearance by 14% (p less than 0.001). Warfarin's apparent volume of distribution was not affected. Further, the effect of erythromycin was greatest among subjects whose control phase warfarin clearance was relatively slow, and least among those whose control phase warfarin clearance was relatively fast. The magnitude of the decrease in warfarin clearance correlated negatively with control warfarin clearance (r = -0.89, p less than 0.005). These data are consistent with the interpretation that erythromycin can potentiate warfarin-induced hypoprothrombinemia by slowing warfarin clearance.

Adult↗
PubMed1984

Selectivity of cholestyramine treatment on hepatic mixed function oxidase activity.

The possibility that oral cholestyramine treatment might indirectly increase hepatic drug oxidations was investigated in rats using pentobarbital, antipyrine, zoxazolamine, and aminopyrine as probes of the hepatic mixed function oxidase system and in humans using amobarbital and antipyrine as probes. Cholestyramine pretreatment of rats for 5 days (87.5 mg/kg twice daily by stomach tube) shortened pentobarbital sleep times, decreased antipyrine-induced hypothermia, but did not influence either zoxazolamine paralysis times or the in vitro N-demethylation of aminopyrine. Neither pentobarbital nor antipyrine pharmacokinetics in rats were affected by the cholestyramine pretreatment. Similarly, in two-way crossover studies with human subjects, a 5-day oral cholestyramine pretreatment (4 g 3 times daily) had no demonstrable effect on the pharmacokinetics of single doses of amobarbital (200 mg i.v.) or antipyrine (500 mg per os). After cholestyramine pretreatment, a trend toward diminished CNS depression produced by amobarbital was observed, but the effect was not statistically significant. The results suggest that hepatic mixed function oxidases in rats for which aminopyrine, antipyrine, pentobarbital, and zoxazolamine are substrates and that hepatic mixed function oxidases in humans for which amobarbital and antipyrine are substrates are not significantly affected by cholestyramine pretreatment.

Adult↗
PubMed1984

Single dose phenytoin clearance during erythromycin treatment.

The effects of erythromycin on the single dose kinetics of phenytoin (PHT) were studied in eight healthy, male volunteers in a crossover study. PHT was administered in a single, oral 300 mg dose either alone or after 5 days of a 7 day erythromycin regimen. Erythromycin base (333 mg) was taken orally every 8 hr. PHT concentrations were measured in plasma collected at 0, 2, 4, 8, 12, 24, 36, and 48 hr after PHT administration and in saliva at 48 hr. PHT was assayed by a polarized immunofluorescent technique. Mean (+/- SD) control values for PHT intrinsic clearance, CLint/F; volume of distribution, V/F; and half-life, t 1/2 were 0.028 (+/- 0.009) 1 X hr-1 X kg-1, 0.97, (+/- 0.33) l/kg, and 27.3 (+/- 12.4) hr, respectively. During erythromycin treatment CLint/F was 0.026 (+/- 0.011) 1 X hr-1 X kg-1, V/F was 0.87 (+/- 0.23) l/kg, and t 1/2 was 31.2 (+/- 26.1) hr. None of the mean values changed significantly due to erythromycin treatment (p greater than 0.05). Estimates of intrinsic unbound PHT clearance, CL'int/F, based upon the 48 hr salivary PHT values were 0.403 (+/- 0.170) 1 X hr-1 X kg-1 and 0.352 (+/- 0.152) 1 X hr-1 X kg-1 for the control and erythromycin phases, respectively (p greater than 0.05). When intrinsic unbound PHT clearance, CL'int/F, was calculated from CLint/F using a mean free PHT fraction, fu, of 0.069 a good correlation between CL'int/F and CL'int/F could be shown. Evaluation of the interaction on the basis of multiple plasma sample data and single salivary sample data led to the same conclusion. Even though erythromycin failed to significantly decrease mean PHT clearance, occasionally large changes in PHT clearance accompanying erythromycin treatment provide sufficient incentive to closely monitor patients taking both drugs.

Adult↗
PubMed1983

Interaction between warfarin and erythromycin.

In the patient described, marked exacerbation of the hypoprothrombinemic response to warfarin coincided with the addition of erythromycin to the drug regimen. A subsequent study in rats provided evidence that erythromycin is capable of increasing the anticoagulant response to single doses of warfarin. On the basis of case findings, preliminary laboratory data, and related clinical data we conclude that the interaction between warfarin and erythromycin is one of potential significance.

Animals↗
PubMed1983

Monitoring phenytoin in salivary and plasma ultrafiltrates of pediatric patients.

The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a gas-liquid chromatography procedure. The phenytoin free fraction among pediatric epilepsy patients not taking valproic acid was normally distributed with a mean (+/- SD) of 9.2 +/- 1.8%. The mean (+/- SD) free phenytoin fraction among patients also taking valproic acid was 13.2 +/- 4.5%. Salivary ultrafiltrates exhibited a close correspondence with plasma ultrafiltrate concentrations, and the ratio of salivary to plasma ultrafiltrate concentrations was 1.06 +/- 0.15. Substantial intraindividual variation in the phenytoin free fraction and the increase in free fraction among patients on valproic acid emphasize the importance of using plasma unbound levels for monitoring phenytoin. The close agreement between plasma and salivary ultrafiltrate concentrations suggests that the latter will provide a practical noninvasive means of monitoring phenytoin.

Adolescent↗
PubMed1983

Effects of triiodothyronine and nutritional status on nuclear non-histone proteins of the rat liver.

UNLABELLED: In the hepatic nucleus of the rat at least 2 nuclear globulin bands, identified by SDS polyacrylamide gel electrophoresis, are known to be influenced by thyroid hormones. In the present article a quantitation of these bands was obtained by scanning techniques. The effects of T3 were studied in male thyroidectomized (Tx) and intact rats. After sacrifice the hepatic nuclear globulins were prepared according to published methods. In Tx rats substituted with a single dose of 50 micrograms or during one week 2 micrograms T3 the t band decreased from 5.3% to 2.7% of the total nuclear globulin content which represent a complete normalisation. The n band did not show this rapid response to T3 as 2 micrograms given for one week only partially restored this band (Tx 1.4%, Tx + T3 2.2%). However during starvation of intact rats only the n band was slightly influenced by T3 as 2 micrograms of T3 partially prevented the decrease of this band seen in untreated euthyroid starving rats. The increase of the t band in starvation was not affected by T3. IN CONCLUSION: the n and t bands are controlled by several factors, two of which are T3 and nutrition. The control of the t band seems to be dominated by the nutritional status of the animal. T3 seems to keep some activity on the n band, even in starved rats.

Animals↗
PubMed1983

Nitrate-induced orthostatic hypotension and long-term circulatory adaptation.

Acute and initial treatment with ISDN provokes arterial hypotension and orthostatic dysregulation which may persist over a period of 10 h. Collapse as a potential risk has to be taken into account in the initial phase of nitrate therapy. During chronic medication, nitrate-induced drop in arterial blood pressure and orthostatic hypotension cannot longer be seen even after high-dose application of ISDN. From a therapeutic point of view these results indicate adaptation of blood pressure regulation to chronic nitrate therapy which is unrelated to potential tolerance in the venous system.

Adaptation, Physiological↗
PubMed1983

Assessment of sublingual isosorbide dinitrate and intracoronary nifedipine during ergonovine provocation.

In 37 patients with suspected vasospastic angina diagnostic ergonovine testing was used as a method of analysing the efficacy of sublingual ISDN in comparison with sublingual and intracoronary nifedipine on coronary luminal diameter, left ventricular ejection fraction, aortic blood pressure, heart rate and left ventricular end-diastolic pressure. 10 mg of sublingual ISDN counteracted the ergonovine effects on left ventricular pump function and hemodynamics. The luminal diameter of the epicardial coronary arteries increased from 3.5 +/- 0.8 to 4.9 +/- 0.8 mm. 20 mg of sublingual nifedipine did not change the coronary luminal diameter within 8-10 minutes after the ergonovine test. After administration of 0.1 mg of nifedipine into the right and left coronary artery the luminal diameters increased in the same range as after sublingual ISDN. Whereas the aortic blood pressure decreased after intracoronary nifedipine from 170 +/- 23 to 153 +/- 27 mmHg with a concomitant increase in heart rate, no effect on the left ventricular pump function could be assessed. In the model of ergonovine testing ISDN has shown itself as a potent drug in releasing the ergonovine effects. Sublingual ISDN is as potent as intracoronary nifedipine in releasing the ergonovine-induced reduction of coronary luminal diameters and more potent in counteracting the ergonovine effects concerning the cardiac pump function.

Adult↗