Plasma levels and urinary excretion of lormetazepam (Noctamid ®-ampoules; 2 mg/10 ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.) administration of the drug to five patients with cirrhosis of the liver (C) and to five young male volunteers (N).

The purpose of this randomized controlled trial was to evaluate the analgesic efficacy of a series of applications of sulfurated mud baths in outpatients suffering from back pain. Within 2 weeks 13 patients took 6 sulfurated mud baths (group A) and 12 patients 6 tap water baths (group B) at home. Before the bath and over 48 h after starting the 1st and the 6th bath, pain intensity was evaluated by the patients according to a visual analogue scale (VAS). The main outcome parameter was the weighted (for time of observation) sum of pain intensity (SPI) after the 6th bath. The mean SPI in group A was 741 mm x h (95% CI 594-864 mm x h) and in group B 1,112 mm x h (95% CI 929-1,252 mm x h) (p = 0.009), suggesting a significantly stronger analgesic effect of a series of sulfurated mud baths than of a series of tap water baths.

s: Fourth International Congress of Therapeutic Drug Monitoring and Clinical Toxicology Vienna, Austria September 4–8, 1995: Poster Session I: Clinical Toxicology/Therapeutic Drug Monitoring: PDF Only

The biliary excretion and apparent oral clearance of metoclopramide (MCL) were determined after oral administration of 1 mg MCL/kg body weight to 10 patients suffering from extrahepatic cholestasis with nasobiliary tube for drainage of the common bile duct. A bilioduodenal endoprosthesis was subsequently fitted in 6 of these patients, i.e. the enterohepatic circulation was restored, and the apparent oral clearance was re-determined.

The antiemetic effect of oral medium-dosed metoclopramide (MCL, 3.5 mg/kg b.w./cycle) and placebo for chemotherapy-induced emesis of a noncisplatin regimen was assessed for inpatients and outpatients in two double-blind placebo-controlled sequential analyses according to Bross (1952). MCL was given in 5 single doses of 0.7 mg/kg b.w. at 0 h (loading) and at 2 h (i.e. start of chemotherapy) and 6, 10 and 14 h (as maintenance doses). Both studies ended after 8 sequential pairs in favor of MCL (2 alpha = 2 beta = 0.05). Major antiemetic protection (< 2 emetic episodes per 26 h) was achieved for 8/8 of inpatients and 7/8 of outpatients (placebo 0/8 and 0/8). Side effects neither required discontinuation of the antiemetic regimen nor additional therapy. The median of MCL plasma levels ranged from 150 to 750 ng/ml and terminal half-lives from 3.9 to 8.9 h.

The pharmacokinetics of lormetazepam (LMA) was studied in five patients with intact and interrupted enterohepatic recirculation (EHR) after an oral dose of 0.03 mg/kg given as solution. The disposition of lormetazepam in plasma was characterized by peak plasma levels of 14-60 ng/ml after 20-40 min. Peak plasma levels of the unchanged drug were higher (p less than 0.05) in case of interrupted EHR as compared to intact EHR. The areas and the plasma levels vs time curves of lormetazepam and its glucuronide were not statistically different and the oral clearance of lormetazepam was similar in both parts of the study (median 3.1 and 3.6 ml/min/kg). In case of interrupted EHR, 23-58% of dose was excreted as lormetazepam and its glucuronide with the urine during 24 h, in case of intact EHR, the urinary dose fraction was 9-35% (p less than 0.05). The 24 h postdose-bile fraction contained only 0.3-2.8% of the oral lormetazepam dose in form of the drug and its glucuronide. In conclusion, only negligible amounts of lormetazepam are excreted in bile. The demethylated metabolite lorazepam was not detectable in the biological samples investigated.

Die Häufigkeit der Behandlung von Übelkeit und Erbrechen als Folge von Krankheitszuständen, die mit gastrointestinalen Motilitätsstörungen einhergehen, steigt ständig (Reynolds 1989). Im folgenden soll die pharmakologische Wirkungsweise und die klinische Anwendung einiger bekannter Verbindungen dargestellt werden. Darüber hinaus soll ein Einblick in die Zusammenhänge von Motilitätsstörungen und Übelkeit bzw. Erbrechen gegeben werden. Schließlich sollen Ergebnisse von pharmakologischen Neuentwicklungen dargestellt werden, die selektiver gegenüber Motilitätsstörungen einerseits und gegen starke Übelkeit und Emesis andererseits eingesetzt werden können.

The correlations between the physicochemical properties (n-octanol-buffer partition coefficients, P) of two series of N-alkylated and ring alkylated beta-adrenoceptor blocking phenoxypropanolamines and their antiarrhythmic activities were studied. For this purpose dose-response curves of the influence on the ventricular arrhythmia threshold (VAT) and on heart rate (HR) were determined in the anaesthetized guinea pig. The degree of N-alkylation correlated with the potency of the drugs to raise VAT and to lower HR. Intraventricular conduction was likewise depressed. Increasing ring alkylation did not consistently further increase biological activity. The combined data from series of drugs showed statistically significant parabolic correlations between hydrophobicity (log P' for pH 7.4) and the biological responses. It is concluded that the nonspecific antiarrhythmic and negative chronotropic activity of the investigated beta-adrenoceptor blocking drugs largely depend on their lipophilic properties. In addition steric and pharmacokinetic factors may be operative.

Single dose studies were performed with three different dosage forms of metoclopramide (0.25 mg/kg body weight) in patients with normal liver function (i.v. (Paspertin): n = 4, oral liquid preparation: n = 4, rectal micro-enema n = 4) and patients with histologically confirmed cirrhosis of the liver (i.v.: n = 6, oral liquid preparation n = 4, rectal micro-enema: n = 8). Drug plasma-concentrations were measured over 8 h by a specific gas chromatographic method. The median areas under the plasma concentration-time curves (AUC0-8) after i.v. and rectal administration were similar in both groups. In contrast, the median oral bioavailability was considerably higher in patients with cirrhosis of the liver (82%) than in patients with normal liver function (60%). It can be concluded from this study, that dosage adjustments may be necessary in oral treatment of patients with cirrhosis of the liver, especially if prolonged therapy is required.