Influence of mexiletine on caffeine elimination.

In an acute experiment in healthy volunteers and in patients under long-term treatment for cardiac arrhythmias, mexiletine inhibits caffeine elimination by about 50%. The clearance of mexiletine is not influenced by caffeine. Some side effects of mexiletine may possibly at least partially be attributable to a retention of caffeine.

Quantitative analysis of common anaesthetic agents.

A summary of chromatographic (e.g. gas chromatography, high-performance liquid chromatography) and non-chromatographic (e.g. radioimmunoassay, enzyme-multiplied immunoassay) analytical techniques suitable for the quantitative analysis of the most popular inhalational (halothane, methoxyflurane, enflurane, isoflurane and nitrous oxide), intravenous (barbiturate, benzodiazepines, etomidate, althesin, morphine, fentanyl, alfentanil, sufentanil, droperidol and ketamine) general and amide-type local (lidocaine, mepivacaine, etidocaine and bupivacaine) anaesthetic agents and some of their metabolites, in biological material, is described. In the case of inhalational anaesthetics attention is also payed to pollution measurement and breath-to-breath monitoring.

Bradycardia due to biperiden.

In a 38-year-old male patient suffering from a severe postzosteric trigeminal neuralgia, intravenous application of 10 mg biperiden lactate led to a long-lasting paradoxical reaction characterized by considerable bradycardia, dysarthria, and dysphagia. The heart rate was back to normal within 12 hours upon administration of orciprenaline under cardiac monitoring in an intensive care unit. Bradycardia induced by biperiden is attributed to the speed of injection and to a dose-related dual effect of atropine-like drugs on muscarine receptors.

[Methohexital clearance in patients with acute hepatitis (author's transl)]. / Plasmaclearance von Methohexital bei akuter Hepatitis. Einfluss einer Behandlung mit essentiellen Phospholipiden oder Phenobarbital.

Pharmacokinetics of methohexital were studied in patients with acute hepatitis and after a treatment period either with "essential phospholipids" or phenobarbital. During the acute phase the distribution of methohexital was significantly altered. No change had been observed in the methohexital clearance. During remission the distribution of methohexital was in a normal range. After treatment with phenobarbital the methohexital clearance increased significantly whereas no change was observed after treatment with "essential phospholipids".

Influence of smoking on caffeine elimination in healthy volunteers and in patients with alcoholic liver cirrhosis.

The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.

[Lidocain clearance after oral and intravenous application in rats with low grade ANIT-cholestasis and galactosamine-induced hepatitis (author's transl)]. / Orale und intravenöse Clearance von Lidokain bei Ratten mit leichter Anit-Cholestase und Galaktosaminhepatitis.

Each of 6 rats with a low grade of ANIT-cholestasis and a low grade of GalN-hepatitis received either 3 mg Lidocain i.v. or 24 mg Lidocain orally. The plasma concentrations of Lidocain were measured over a period of 3 1/2 hrs. The systemic clearance of Lidocain (Cli.v. = Di.v. divided by AUCi.v.) was significantly increased on ANIT-cholestasis (17 +/- 3) and GalN-hepatitis rats (13 +/- 2) (control rats: 7 +/- 1 ml/min x 100 g bw). Oral clearance of Lidocain (Clor = Dor divided by AUCor) was not significantly different in the three respective groups. In both groups with experimental liver disease the hepatic blood flow--calculated by comparing the systemic to the oral clearance--was significantly increased (22 +/- 4 and 19 +/- 3 vs 8 +/- 1 ml/min x 100 g bw). Due to this increase, the hepatic extraction ratio of Lidocain was significantly decreased (ANIT-cholestasis 0.73 +/- 0.07; GalN-hepatitis 0.74 +/- 0.05; controls 0.85 +/- 0.03). Because of an increase of systemic Lidocain clearance, no toxic plasma concentrations were observed.

Simultaneous determination of blood concentrations of methohexital and its hydroxy metabolite by gas chromatography and identification of 4'-hydroxymethohexital by combined gas--liquid chromatography--mass spectrometry.

A simple, sensitive and selective method is described for the simultaneous determination of low concentrations (less than 50 ng/ml) of underivatized methohexital and its hydroxy metabolite in small (0.1 ml) samples of human and rat plasma or whole blood by gas chromatography with nitrogen-selective detection. Moreover, the main metabolite in rat and man was identified as 4'-hydroxymethohexital by comparison of chromatograms from gas--liquid chromatography (GLC) with data obtained from GLC--mass spectrometry and 1H-nuclear magnetic resonance spectrometry of this metabolite, produced both by incubating methohexital with isolated rat liver microsomes and by isolating this metabolite from rat urine.

[Drug metabolism in patients with liver disease (author's transl)]. / Arzneimittelmetabolismus bei Patienten mit Lebererkrankungen.

Patients with acute hepatitis and patients with compensated or decompensated cirrhosis of the liver have a decreased plasma clearance of hexobarbital. This however could not been demonstrated in patients with intra- or extrahepatic cholestasis and patients with primary biliary cirrhosis of the liver. The plasma clearance of methohexital, - a high clearance drug - is not changed in the same way. Also there is no evidence as yet, that patients with liver disease and without a collateral portal circulation do have an increased bioavailability of oral high clearance drugs.