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Biomedical subjects

P Altmayer

Publications and source records attributed to P Altmayer.

At least 37 records · Page 2Linked to original sources

pH-dependent interaction of halothane upon thiopental binding to human serum albumin.

At pH 7.4 the binding of thiopental to human serum albumin (HSA) was increased in the presence of halothane. In order to obtain information about the mechanism of this interaction, in vitro binding experiments by means of equilibrium dialysis were carried out at different pH values. At pH 4.97 the binding of thiopental to HSA 1% was low (23% bound) and not influenced by halothane. An increase of thiopental binding caused by halothane could be seen at pH 7.4 (55% bound vs. 41% in the control = without halothane) and at pH 8.23 (62% vs. 54%). At pH 10.15 an opposite interaction was found: in the presence of halothane thiopental binding was considerably decreased (36.2% vs. 47.0% in the control). Evaluation of the binding parameters of experiments using increasing substrate concentrations (Scatchard plot) revealed quite different changes of the two classes of binding sites of HSA for thiopental. It is assumed that halothane causes reversible conformational changes of the albumin molecule resulting in altered binding characteristics for thiopental.

Binding Sites↗

[A computer-assisted noninvasive monitoring system with graphic display of online determination of cardiovascular parameters].

During anesthesia the cardiovascular system is usually assessed on the basis of heart rate and arterial pressure, although the most important hemodynamic measurement is that of flow. A method for the non-invasive measurement of cardiac output is based on thoracic electrical bio-impedance. The NCCOM3-R7 is a non-invasive cardiac output monitor that makes use of thoracic electrical bioimpedance, which has been shown to provide results comparable with thermodilution in various hemodynamic states both in animals and humans. A new on-line hemodynamic monitoring system has been developed using the non-invasive NCCOM3-R7 (BoMed) cardiac output monitor, a portable microcomputer (NEC Multispeed) in connection with a software package CDDP-1 (BoMed), a Dinamap automatic arterial pressure monitor (Critikon) and an additional 14" display. Every 16 heart beats the cardiac output monitor transfers 11 cardiodynamic parameters in ASCII-format to the microcomputer, where the data are stored. Using the CDDP-1 program the current cardiodynamic status of the patient is displayed numerically and graphically on the monitor screen. Mean arterial pressure is determined by Dinamap and the data must be entered manually in the menu. The program then calculates systemic vascular resistance and left ventricular work index, the CVP being set to 3 torr and PAOP to 6 torr. In the graphic display the current hemodynamic status is shown and the underlying situation is analyzed in terms of systemic vascular resistance and volume-dependent contractility. The reliability of this on-line monitoring system is demonstrated in a high-risk patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

[Postoperative monitoring following short duration surgery of the ear, nose and throat. Experiences with midazolam as an anesthesia induction agent].

A combination of midazolam and alfentanil was used on 24 patients for induction of general anaesthesia. Anaesthesia was maintained with N2O/O2 and repeated injections of alfentanil. The mean operation time was 40.8 min. At the end of surgery the patients recovered 4.8 min after antagonisation of the alfentanil with naloxon, and the endotracheal tube could be removed. Thirty, 60 and 120 min after extubation the patients were asked to perform a Marschner's test, which measures the ability to concentrate on fast intellectual work. Up to 660 simple arithmetical additions could be checked within 7.5 min. The intellectual performance recovered quickly: after 30 min 79% of the pre-operative values were reached, after 60 min 85% and after 120 min 90%. Midazolam is suitable as an induction agent for shortlasting otorhinolaryngological surgery.

Adolescent↗

The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently.

In man, a change of thiopental pharmacokinetics was observed under halothane anesthesia, but not when patients were anesthetized with enflurane and isoflurane. After an initial subanesthetic dose of 50 mg thiopental, the concentrations in serum (T) were determined over 15 min (4 samples). From these T-values the pharmacokinetic parameters Vc (central volume of distribution), t1/2 alpha and Cl were established (control). 16 min after the first thiopental dose, one of the inhalation anesthetics was administered (randomized). After 45 min exposure to the respective inhalation anesthetic (2-3 MAC in combination with N2O, steady-state a second dose of 50 mg thiopental was injected and the T-values were determined again over 15 min. The T-values of the control course varied considerably; the logarithmic frequency distribution revealed two distinct subgroups of patients, A and B, with characteristic Vc and t1/2 alpha. Both subgroups were influenced by the volatile anesthetics in a similar way with regard to pharmacokinetic parameters. With halothane, Vc was decreased and t1/2 alpha was shortened. In contrast, enflurane and isoflurane did not affect the pharmacokinetic parameters.

Adult↗

Sensitive HPLC assay for thiopental in human serum after simple preparation of the samples. Its application for clinical research.

A simple, precise and sensitive micro method for the determination of thiopental in human serum is presented. After deproteinization with acetonitrile the supernatant was directly injected into a reversed phase HPLC system with UV photometrical detection at 280 nm. The limit for the detection of thiopental was less than 0.1 microgram/ml serum. Time consuming extraction of the serum sample was not necessary. The method can be recommended for clinical routine analysis; its suitability has been demonstrated in several studies.

Chromatography, High Pressure Liquid↗

Disposition of etofibrate, clofibric and nicotinic acid esters, and their products in dogs.

Etofibrate, the ethylene glycol diester of clofibric and nicotinic acids, on intravenous infusion into dogs, has a terminal half-life of 2 min. The intermediate half-esters, the nicotinate and the clofibrate, have respective terminal half-lives of 4.6 and 1.7 min and appear fleetingly when etofibrate is administered. In contrast to the 42-h terminal half-life of clofibric acid, the other final transformation product, nicotinic acid, shows saturable or dose-dependent pharmacokinetics in dogs that conform to the Michaelis-Menten equation with a terminal half-life of 4.4 min at low concentrations (less than 6.9 microM/kg). Three distinct metabolites of nicotinic acid can be identified and assayed chromatographically in the urine. The partition properties were similar to nicotinic acid. Nicotinic acid is excreted 30% unchanged into urine with a renal clearance of 70 mL/min in 27-kg dogs.

Animals↗

[The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate].

Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively.

Administration, Oral↗

Plasmolysis, red blood cell partitioning, and plasma protein binding of etofibrate, clofibrate, and their degradation products.

Etofibrate (I), the ethylene glycol diester of clofibric and nicotinic acids, degrades almost equally through both half-esters with half-lives of approximately 10 and 1 min in fresh dog and human plasma, respectively. The nicotinate V degrades with half-lives of approximately 12 hr and 50 min in fresh dog and human plasma, respectively. Ester III and clofibrate VI degrade by saturable Michaelis-Menten kinetics in fresh human plasma, with similar maximum initial rates and respective terminal first-order half-lives of 12 and 26 min. Tetraethyl pyrophosphate at 100 micrograms/ml inhibited human plasma and red blood cell esterases permitting plasma protein binding and red blood cell partitioning studies. The red blood cell-plasma water partition coefficient was 5.4 for 0.2-80 micrograms/ml of I. Clofibrate (VI) showed a saturable erythrocyte partitioning that decreased from 7.8 (10 micrograms/ml) to 1 (50 micrograms/ml). The strong binding of I and VI to ultrafiltration membranes necessitated the determination of their plasma protein binding by the method of variable plasma concentrations of erythrocyte suspensions to give 96.6% (0.2-80 micrograms/ml) and 98.2% (13.6-108.4 micrograms/ml) binding, respectively. Methods for the determination of the parameters of saturable and nonsaturable plasma protein binding for unstable and membrane-binding drugs by the method of variable plasma concentrations in partitioning erythrocyte suspensions are presented.

Animals↗

Gastric potential difference as a model in clinical pharmacology: assessment of gastric mucosal response to aspirin.

Gastric potential difference in 16 healthy subjects (GPD) was measured on three different days to assess baseline variability. The effect of three different doses of aspirin on PD in 19 additional subjects was determined. Several new parameters are suggested for better description of the GPD changes following ingestion of known gastric irritants. From these parameters, a Reiz Index (RI) was calculated as a single term representing the extent and severity of the GPD response to aspirin. One-way Anova followed by Scheffe comparisons showed significant differences between the mean RI values resulting from the administration of aspirin 250, 500 and 1000 mg.

Aspirin↗

Pharmacokinetics of the immunomodulatory 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethyl-amino-n-propyl)-D-glucofuranose hydrochloride in normal human volunteers.

1,2-O-Isopropylidene-3-O-3'(N',N'-dimethyl-amino-n-propyl)-D-glucofuranose hydrochloride, I, is a substituted sugar with claimed immunomodulatory action. Pharmacokinetic studies in 10 volunteers (bolus i.v., 100 mg) showed respective half-lives for each exponential in the sum of two exponentials that characterized plasma level decay with time of 4.6 +/- 0.4 (SEM) min, t1/2(lambda 1), and 244 +/- 20 min, t1/2(lambda 2)), The total and renal clearances were 277 +/- 20 and 254 +/- 18 (SEM) ml/min, indicative of tubular secretion. Urinary recovery was 93 +/- 2%. The estimated volumes of distribution of the central compartment and overall equilibrated tissues were 14.7 +/- 1.9 and 96 +/- 8 liters, respectively. Sequential daily oral administration of large amounts in capsules (1.2, 2.1, 2.9, 4.1, and 5.0 g) permitted an estimate of 63 +/- 4 (SEM)% bioavailability from urinary recovery of drug, with estimated terminal half-lives of 454 +/- 25 min from minimal data. Orally administered 2.03 g showed a rapid absorption (t1/2 = 10 min) after a lag time of 23 min, and a terminal plasma half-life of 344 min. Plasma protein binding of I was negligible. The erythrocyte/plasma water partition coefficient was close to unity.

Adjuvants, Immunologic↗

[On the pharmacokinetics of tiaprofenic acid and its possible interactions with acetylsalicylic acid and aluminum hydroxide (author's transl)].

To clarify the question whether pharmacokinetic properties of tiaprofenic acid (presumable trade name Surgam) can be changed by simultaneous application of aluminum hydroxide or acetylsalicylic acid (ASA) a randomized study of 7 healthy volunteers was carried out. The results show that the bioavailability as well as the pharmacokinetic profile of orally administered tiaprofenic acid is not changed by the mentioned compounds.

Aluminum Hydroxide↗

[Experience with vaginal suppositories containing chemotherapeutic agents (author's transl)].

The authors determined the release of chloramphenicol, oxytetracycline, neomycin and sulphadimidine from different bases (polyoxethene mass, solid fat, 95% solid fat +5% Span 20). The diffusion of chloramphenicol and sulphadimidine was best from hydrophilic bases; that of oxytetracycline and neomycin, from emulsifier-containing lipophil bases. This may be explained by the solubilities of the pharmaca and by interactions between base and active substance.

Anti-Infective Agents↗

[Measuring the potential difference of gastric mucosa as a means of quantifying the protective effect of Al-acetylglycyrrhetinate after a dose of acetylsalicylic acid (author's transl)].

A clinical pharmacological model to measure the potential difference of the gastric mucosa is reported. The model partially from literature derived has been further developed mathematically. An irritation index is reliable to quantify the protective function of chemical agents. In the reported study Al-acetylsalicylic acid (ASA): The measured parameters (Pdmax, AUB) show that the irritation of the gastric mucosa induced by ASA can be reduced if 100 mg Al-acetylglycyrrhetinate has been predosed. After the instillation of 1000 mg ASA the mean Pdmax amounts to 27.20 [mV] (s = 9.63), the AUB to 930.60 [mV . mins] (s = 311.10). After pre-treatment with Al-acetylglycyrrhetinate the irritation of ASA only produces a Pdmax of 17.80 [mV] (s = 986) and and AUB of 678.60 [mV . min] (s = 374.11). The differences of Pdmax and AUB are significant on the 5% level. The irritation index for 1000 mg ASA amounts to 27.5 [mV2 . min], after pre-treatment with 100 mg Al-acetylglycyrrhetinate it decrease to 14.9 [mV2 . min].

Adult↗

[Limitations and possibilities in the determination of transmural gastric potential in humans].

"Determination of the Transmural Gastric Potention, Limitations and Possibilities" presents a new approach for measuring the transmural gastric potential difference with computerized calculations of parameters. A "Reizindex" is introduced as a new secondary parameter describing the process of irritation better than Pdmax or area or area under the baseline. A second secondary parameter the "mean instability time of the membrane" is also introduced as a very stable parameter as far as the whole process is concerned. (first moment) The relevance of the model is proved by baseline data of 16 volunteers and investigations with a strong H2-blocker.

Electrochemistry↗

[Circadian-induced change in the pharmacokinetic pattern exemplified on hexobarbital/Retrospective analysis of experimental data (author's transl)].

The present study dealt with data from a study to evaluate circadian influences on the pharmacokinetics of hexobarbital. It could be seen that the pharmacokinetic model changes from an open one-compartment model to an open two-compartment model in dependence of the time of application. The curve fitting to an open two-compartment model reached high correlations when the test substance was applied at 18 h. The pharmacokinetic parameters to be evaluated did not fit to literature data. After application of the substance at 10 h in the morning the curve fitting to an open one-compartment model correlated highly. The pharmacokinetic parameters at this time comparable with the known literature.

Circadian Rhythm↗

[Circadian fluctuations of pharmacokinetic parameters after oral administration of hexobarbital (author's transl)].

To 4 male and 2 female subjects hexobarbital was applied orally at different times of the day: 2, 10, 18 h. Serum concentrations of hexobarbital were determined by HPLC procedure and the resulting pharmacokinetic parameters in a rotating iterative program. Application at 18 h resulted in a shorter invasion time, a higher maximum concentration and a delayed elimination; in addition, the AUC was elevated in relation to application at 2 or 10 h. In the 2 female subjects a different pattern was observed. The results lead to the assumption that application of hexobarbital is more effective in the evening than in the morning.

Adult↗