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Biomedical subjects

R Gugler

Publications and source records attributed to R Gugler.

At least 73 records · Page 4Linked to original sources
PubMed1984

[Relevant inhibition of acetylcholinesterase with H2-receptor antagonists].

An inhibition of acetylcholinesterase activity by ranitidine and cimetidine as described by Hansen and Bertl (Z. Gastroenterol. 21: 164, 1983; Arzneimittelforsch. 33: 161, 1983) could only be confirmed by use of 1000-fold higher concentrations of the H2-antagonists (ID50 for ranitidine: 3,2 X 10(-4) M, for cimetidine: 3,1 X 10(-2) M) than those reported by the authors. The discrepancy may be explained by the fact that the authors did not consider the dilution factor in their method. In a typical therapeutic situation in 8 patients with ranitidine 150 mg twice daily and cimetidine 400 mg twice daily an inhibiton of the acetylcholinesterase could not be demonstrated. The inhibition of the acetylcholinesterase activity by H2-antagonists is of no practical relevance.

Acetylcholinesterase↗
PubMed1984

Cimetidine disposition in obesity.

Cimetidine pharmacokinetics were studied in 13 otherwise healthy but obese volunteers, having a mean body weight of 113 kg and a mean percentage ideal body weight (IBW) of 179%. Sixteen healthy volunteers of normal body habitus (64 kg, 99% IBW) served as controls. All subjects had normal renal function and no laboratory or clinical evidence of hepatic or cardiac dysfunction. After administration of 200-300 mg of cimetidine by rapid intravenous injection, multiple plasma samples obtained over the next 24 h were analyzed for cimetidine concentration by high pressure liquid chromatography. Elimination half-life was not different between obese and control subjects (2.23 versus 2.08 h). Apparent volume of distribution was also similar between subject groups (120 versus 106), as was total metabolic clearance (616 versus 579 ml/min). Using percentage IBW as a measure of obesity, no relationship was found between percentage IBW and apparent volume of distribution (r = 0.29). Cimetidine similarly distributes into IBW in both obese and normal weight subjects, and there is minimal distribution of cimetidine into excess body weight over IBW. Furthermore, there is no difference in total metabolic clearance or half-life of cimetidine between obese and control subjects. Cimetidine dosage in clinical practice should therefore be calculated on the basis of IBW, which better reflects lean body mass, instead of total body weight, which reflects adipose tissue weight in addition to lean body mass.

Adult↗
PubMed1983

Cimetidine impairs nitrazepam clearance.

The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t1/2 from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.

Adolescent↗
PubMed1983

Single- and multiple-dose metronidazole kinetics.

Kinetics of metronidazole and its metabolites were examined after single oral and intravenous doses and multiple oral doses in seven subjects by a sensitive HPLC assay. After 400 mg metronidazole IV, mean Vd beta was 1.05 l/kg. Mean plasma t1/2 was 8.3 hr with a ClTBC of 1.31 ml/min/kg. Clearance to the major metabolites, 2-hydroxy-metronidazole and 1-acetic acid metronidazole, accounted for over 90% of the ClTBC. After a single oral 400-mg metronidazole dose, the development of peak metronidazole plasma concentrations of 6.9 micrograms/ml averaged 2.3 hr after dosing. Systemic oral bioavailability was complete (98.9%). During twice-daily multiple metronidazole dosing, 400 mg, metronidazole kinetics were the same. Elimination t1/2 was 8.3 hr and average predicted steady-state metronidazole concentrations during one dosing interval (6.3 +/- 0.5 micrograms/ml; mean +/- SE) were equal to the observed concentrations (6.9 +/- 1 micrograms/ml). Urinary excretion of unchanged metronidazole was below 10% of the total dose. Seventy-five percent of the dose was 2-hydroxy-metronidazole and 1-acetic acid metronidazole, and 15% was conjugates of metronidazole and 2-hydroxy-metronidazole.

Administration, Oral↗
PubMed1983

[Surgical treatment of ulcer disease 5 years before and after the introduction of cimetidine].

To determine whether H2-antagonists have changed type and frequency of operations for peptic ulcer, all operations of the one hospital of a city with a population of 80 000 were analysed. The total number of operated patients decreased after cimetidine from 425 to 278 (35%). The ratio of male to female patients was 3:1 in either period. While the decrease in elective operations of uncomplicated ulcer was 51%, operations in patients with ulcer complications (bleeding, perforation, stenosis) decreased by only 9%. The decrease was above average in Billroth I and Billroth II gastrectomy, but the number of patients with selective vagotomy increased 3-fold. The number of operations decreased by 40% for duodenal ulcer and by 20% for gastric ulcer. Of all ulcer complications bleeding decreased by 31%, the number of perforations was unchanged, but the number of patients with stenosis increased by 58%. Overall mortality decreased from 25 in the initial to 20 in the subsequent five year period. Twenty and 19 patients, respectively, died with complicated ulcer disease (12,5% of all operations), mortality was 6 (1,5%) with operations for uncomplicated ulcer.

Cimetidine↗
PubMed1983

[Metabolic effects of antacids and interactions with other drugs].

The incidence of side effects from antacids is low, but patients with renal insufficiency are at risk to develop alkalosis with high doses of calcium carbonate or magnesium hydroxides, or to develop hypercalcemia due to insufficient calcium elimination by the kidneys.--A great potential exists for drug interactions with antacids. In most instances, the effectiveness of other drugs is decreased in the presence of antacids, but effectiveness may be increased for L-dopa (less degradation in stomach) or quinidine (renal elimination reduced). Interactions at the absorption level can be avoided by administering the antacid one hour after intake of the other drugs (one hour after meals) which is also the optimum dosing schedule to ensure good antacid effect. Interactions through changes of urine pH are not eliminated by observing special dosing time schedules, but by modifying the dose or by selecting alternative drug treatment.

Absorption↗
PubMed1982

[Treatment failure of cimetidine in duodenal ulcer (author's transl)].

Acid secretion was measured after a six-week standard treatment with cimetidine in ten patients each with healed or non-healed duodenal ulcer, and the drug's pharmacokinetics studied. There was no difference between the two groups with respect to fasting concentration of cimetidine (compliance), the area under the plasma-level curve, as well as renal excretion (bioavailability) and the period of effective plasma concentration. Maximal secretion during cimetidine treatment was also identical in the two groups. On the other hand, basal secretion in the group of treatment failure was significantly increased (P less than 0.05). Basal secretion during administration of cimetidine can be used as a prognostic criterion for the healing of duodenal ulcer.

Biological Availability↗
PubMed1982

Prediction of bioavailability for drugs with a high first-pass effect using oral clearance data.

For drugs with a high hepatic clearance, bioavailability is low due to the so-called "first pass effect". Prediction of the bioavailability for these drugs has been only loosely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.

Administration, Oral↗