Pharmacology and preclinical pharmacokinetics of peppermint oil.

The principal pharmacodynamic effect of peppermint oil relevant to the gastrointestinal tract is a dose-related antispasmodic effect on the smooth musculature due to the interference of menthol with the movement of calcium across the cell membrane. The choleretic and antifoaming effects of peppermint oil may play an additional role in medicinal use. Peppermint oil is relatively rapidly absorbed after oral administration and eliminated mainly via the bile.

Gastrointestinal clinical pharmacology of peppermint oil.

In nine studies, 269 healthy subjects or patients underwent exposure to peppermint oil (PO) either by topical intraluminal (stomach or colon) or oral administration by single doses or 2 weeks treatment (n = 19). Methods used to detect effects were oro-cecal transit time by hydrogen expiration, total gastrointestinal transit time by carmine red method, gastric emptying time by radiolabelled test meal or sonography, direct observation of colonic motility or indirect recording through pressure changes or relieve of colonic spasms during barium enema examination. The dose range covered in single dose studies is 0.

Peppermint oil in irritable bowel syndrome.

In a literature search 16 clinical trials investigating 180-200 mg enteric-coated peppermint oil (PO) in irritable bowel syndrome (IBS) or recurrent abdominal pain in children (1 study) with 651 patients enrolled were identified. Nine out of 16 studies were randomized double blind cross over trials with (n = 5) or without (n = 4) run in and/or wash out periods, five had a randomized double blind parallel group design and two were open labeled studies. Placebo served in 12 and anticholinergics in three studies as comparator.

[Economizing potential in rehabilitation--through targetted patient selection].

Major economies need to be made in the health care system. The austerity legislation effective as of January 1, 1997 will result in considerable benefit cuts in the statutory health and pension insurance schemes, with major repercussions also in the field of rehabilitation. Possible devices for realizing potential economies are more precise targetting in patient selection, upgrading social-medical expertise, as well as adjusting rehabilitation more precisely to both patients' needs and economical service delivery.

[Early rehabilitation in the hospital].

For years, experts have been demanding that early rehabilitation in the hospital be improved upon. They argue that timely and on-target activation and mobilisation of the patient while he or she is still under inpatient treatment will often enable earlier initiation of the subsequent comprehensive rehabilitation measures. Early start of rehabilitation improves the chances of social re-integrations.

Kinetics of piretanide tablets, penbutolol tablets and the fixed combination of both drugs in healthy male subjects after a single oral dose.

In an open-labelled cross-over study, ten healthy males received an oral dose of piretanide (6 mg tablet), penbutolol (40 mg film-coated tablet) or the fixed dose combination (film-coated tablet). Serum pharmacokinetics and 48 h urinary excretion of each drug were determined for the three dose regimens. The serum pharmacokinetics and excretion of penbutolol were unchanged in combination with piretanide.

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin.

Kinetics of piretanide absorption from the gastrointestinal tract.

In a recent report, it was shown that the loop diuretic piretanide is rapidly absorbed after placement of a piretanide solution in the duodenum, while the rate of absorption is definitely slower when the drug is instilled into the ascending colon (5). When piretanide is instilled into the stomach, the absorption process does not differ significantly from that after placement in the duodenum, neither with respect to amount nor rate (5). However, it was not clear from this study whether piretanide is directly absorbed from the stomach or rapidly released into the duodenum.

A new aspect of serum protein binding of tolbutamide.

Tolbutamide is known to bind highly to serum proteins. Quite different values have, however, been reported for binding, ranging from 80 to 99 percent. In this study, in vivo and in vitro binding of increasing concentrations of tolbutamide to human serum proteins were evaluated.

Cefodizime penetration into skin suction blister fluid following a single intravenous dose.

Cefodizime pharmacokinetics was investigated, evaluating drug concentrations in serum, skin suction blister fluid (SBF), saliva and urine in six healthy male subjects who were administered a 1-g dose intravenously. Serum levels in five subjects can be described according to a two-compartment open model; terminal half-life is 181 +/- 14 min. Volume of distribution (Vd beta) amounts to 15.

The absorption of piretanide from the gastro-intestinal tract is site-dependent.

The absorption of piretanide was investigated after placing the drug in the stomach, duodenum and ascending colon under visual control. The relative amounts absorbed and the rates of absorption were estimated from the area under the curve and the total mean time, respectively. Similar amounts of piretanide were absorbed and at almost the same rate after placement in the stomach and duodenum; the area under the curve for the stomach was 250 ng h/ml and for the duodenum 243 ng h/ml, the mean absorption times being 1.

Effects of piretanide on potassium balance in hypertension.

Ten hypertensive patients completed a trial lasting 12 weeks to measure the effect of long-term treatment with piretanide, a new, powerful 'loop' diuretic, on total body potassium (TBK). After 2 weeks of placebo treatment, they received 6 mg piretanide twice daily. This dose was increased to 6 mg 3 times a day if blood pressure was not satisfactorily lowered after 4 weeks.

Absorption of glibenclamide from different sites of the gastro-intestinal tract.

In a study of eight volunteers and six patients, glibenclamide was placed at different sites of the gastro-intestinal tract under visual control. The dose was instilled once into the stomach and once into the duodenum of the eight volunteers in a randomized crossover design. The six patients underwent diagnostic colonoscopy, and the dose was placed into the ascending colon if pathological findings were not present.

[Effect of forskolin eyedrops on intraocular pressure in healthy males].

Suspensions of Forskolin in concentrations of 0.3; 0.6; and 1.

Effects of tendamistate on postprandial plasma glucose, free fatty acid and triglyceride levels.

A dose of 400 mg tendamistate or a placebo was given to 10 volunteers in order to investigate its effects on plasma glucose, free fatty acid and triglyceride levels after a porridge meal. Each subject participated in two phases, in each of which they ate porridge prepared from 100 g maize meal together with either placebo or tendamistate 400 mg. Serial blood specimens for plasma glucose determinations were taken up to 3 hours after the meal, and those for free fatty acid and triglyceride determinations up to 14 hours after the meal.

Effects of tendamistate (an alpha-amylase inactivator), guar and placebo on starch metabolism.

Nine volunteers participated in a double-blind, cross-over study to compare the effects of tendamistate (HOE 467), guar and placebo on starch metabolism. In each phase of the trial they received a maize-meal porridge breakfast. They either received 5 g guar granules before the porridge or 100 mg tendamistate mixed with the porridge, or porridge alone.

Pharmacodynamics and tolerability of low doses of tendamistate given with starch.

Six healthy male volunteers participated in a double-blind cross-over study in which 12,5 mg, 25 mg, or 50 mg tendamistate (HOE 467), an alpha-amylase inactivator, or placebo were administered with 100 g maize meal, which contains 85,5 g pure starch. Serial blood specimens for measurement of plasma glucose concentrations, which served as a criterion of starch absorption, were taken up to 3 hours after each starch meal, and side-effects were recorded. The administration of HOE 467 with a starch meal resulted in a significant inhibition of starch absorption.

Inhibition of starch absorption by tendamistate (an alpha-amylase inactivator).

Tendamistate (HOE 467) is an alpha-amylase inactivator. Doses of 100 and 200 mg and a placebo were administered to 6 volunteers in order to investigate the effect of the drug on plasma glucose levels after a bread meal. Each subject participated in three phases, in each of which they received a meal consisting of 200 g white bread together with either placebo or tendamistate 100 or 200 mg.

Effects of tendamistate (alpha-amylase inactivator) on starch metabolism.

Tendamistate (Hoe 467) reduces gastrointestinal absorption of starch by inactivating α-amylase. Two trials were performed to investigate the influence of timing and mode of administration of tendamistate, relative to starch intake, on the pharmacodynamics of the drug. (i) In the first trial 400 mg enteric coated capsules, 400 mg non-enteric coated capsules and placebo were compared in 12 volunteers.

The use of renal enzymes as early indication of renal toxicity after multiple-dose administration of aspirin.

Ten volunteers participated in a study comparing the effects on renal enzymes of multiple oral doses of aspirin relative to no treatment. The total urinary output was collected daily for 21 days from all subjects. The first 7 days were treatment-free.

Pharmacodynamics and urine pharmacokinetics of three doses of piretanide.

Three doses (3 mg, 6 mg and 12 mg) of piretanide, a new high ceiling diuretic, and placebo were given to 8 volunteers to investigate the relationship between the pharmacodynamic parameters, the dose and its urinary excretion. Intake of food and fluid were standardized from 48 h before until 24 h after drug administration. Urinary output, excretion of unchanged drug, and the excretion and clearance of Na+ and K+ were measured hourly for 7 h after treatment.

Pharmacokinetic aspects of the interaction between clobazam and cimetidine.

The pharmacokinetic interaction between clobazam and cimetidine was studied in 9 healthy male volunteers in an open-labelled study. After a single oral dose of clobazam 30 mg, a wash-out period of 14 days was followed by daily doses of cimetidine 1 g for one week. Thereafter a single oral dose of clobazam 30 mg was again given.