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Biomedical subjects

J Kanto

Publications and source records attributed to J Kanto.

At least 163 records · Page 9Linked to original sources

Effect of age on the pharmacokinetics and sedative of flunitrazepam.

Flunitrazepam (0.015 mg/kg) was injected i.v. into 20 patients, ages 19-79 years, as a sedative agent prior to epidural anesthesia. The concentrations of unchanged flunitrazepam in sea were determined by 63Ni-EC-GLC, and the pharmacokinetic parameters were calculated using the two-compartment open model. Age as such had no effect on the kinetics of flunitrazepam, but its sedative effect was clearly increased in the group over 60. No correlation between the serum level or elimination half-life and sedation was found. Generally, flunitrazepam's strong and rapid sedative effect renders it a useful adjuvant in connection with epidural anesthesia.

Adult↗

A comparative study on the clinical effects of flunitrazepam and oxazepam as oral premedication.

The clinical effects of flunitrazepam and oxazepam as oral premedicants were tested in a double-blind study of 69 otorhinolaryngologic patients. Flunitrazepam had a somewhat higher sedative effect (p less than 0.10) and moderated the increase in systolic blood pressure significantly (p less than 0.005) more than did oxazepam, but as regards the other parameters tested no significant differences were found (sleep, apprehension, excitement, dizziness, emetic effect, headache, increase in heart rate, venepuncture). In some patients a profuse salivary secretion was observed despite intravenous injection of atropine just before the induction of anesthesia. Our results support earlier claims of flunitrazepam's relatively strong sedative and anxiolytic properties, but on the whole the difference in clinical effects of these benzodiazepine derivatives was not marked.

Administration, Oral↗

The effect of drugs with different mechanisms of action on the contraction of the human gallbladder.

The effects of drugs with different mechanisms of action on the human gallbladder smooth muscle are reviewed. Sincalide, the C-terminal octapeptide fragment of cholecystokinin, caused a clinically important contraction of the gallbladder during oral cholecystography in 72% of the patients. Within 8-12 min cystic duct visualization occurred in 44% and common bile duct visualization, in 17%. On the other hand, the standard concentration meal (200 ml cream) caused a more reliable gallbladder contraction in 30 min. One tablet of Baralgin, i.v. proxyphylline (300 mg), and i.v. glycopyrrolate (0.2 mg) had no relaxing effect on the contracted gallbladder during oral cholecystography. Similarly, i.v. metoclopramide (20 mg) and i.v. prostaglandin E2 (25, 50, and 75 micrograms) were ineffective, whereas 1 ampule of Baralgin and 1 ampule of Palerol i.v. caused a significant dilatation. Litalgin i.v. 1 ampule, i.v. papaverine (40 mg), and sublingual nitroglycerin (0.5 mg) had a slight relaxing effect on the smooth muscle of the gallbladder. In an acute attack of pain in a patient with gallstones, i.v. administered Baralgin and Palerol seem to be effective; i.v. Litalgin, i.v. papaverine, and sublingual nitroglycerin may be of value in milder biliary tract disorders, but the benefit of i.v. proxyphylline, i.v. glycopyrrolate, and oral Baralgin is questionable. Metoclopramide can be used as an antiemetic drug in patients with gallstones.

Cholecystography↗

Interaction between proxyphylline and salbutamol.

Salbutamol increased significantly the bronchodilating effect of proxyphylline both in experimental animals and in asthmatic patients. In guinea pigs (modified Konzett-Rössler method) the reduction in response to metacholine caused by increasing doses of proxyphylline and salbutamol significantly exceeded that of either drug alone. In a double-blind, randomized cross-over study conducted on 3 consecutive days, asthmatic patients received 500 mg proxyphylline orally three times daily. On the 2nd or 3rd day a significantly greater improvement in the peak expiratory flow was found after the combination of proxyphylline and salbutamol (3 mg p.o.) in comparison with proxyphylline and placebo. Salbutamol had no significant effect on the plasma concentrations of proxyphylline, which varied between 14 and 22 microgram/ml. The combination of oral proxyphylline and salbutamol is clinically useful in increasing drug response without increased adverse effects.

Adolescent↗

Pharmacokinetics of labetalol in healthy volunteers.

The pharmacokinetics of labetalol, a combined alpha- and beta-receptor blocking agent, were studied in eight healthy volunteers. After intravenous injections (n = 4) of 1.5 mg/kg, the drug was rapidly distributed (mean T 1/2 = 4.9 min) and quite rapidly eliminated (mean T 1/2 = 4.9 hrs). The mean total plasma clearance value was 24.80 ml/min/kg. The values for Vdc (mean 1.1 l/kg) and Vdss (mean 9.41 l/kg) indicate extensive extravascular distribution of labetalol. The systemic availability was about 18%. There was a significant correlation between the calculated drug concentrations in the hypothetical compartment 2 and the percentage decreases in blood pressure after the intravenous injection. After a single 200 mg oral dose (solution, non-coated and coated tablets), the tablet formulation had no significant effect on the gastrointestinal absorption. After repeated oral doses of 200 mg twice daily (n = 4), no accumulation in plasma was observed.

Administration, Oral↗

Pharmacokinetics of dihydroergotamine in healthy volunteers and in neurological patients after a single intravenous injection.

The pharmacokinetics of dihydroergotamine (DHE) was studied in healthy volunteers (n = 6) and in neurological patients (n = 12). After a single 1.0 mg intravenous injection (n = 5) DHE quickly disappeared (T 1/2 beta = 32.9 min, Vdss = 0.33 liter/kg, Cltot = 1055.7 ml/min). In saliva (dose 1.0 mg, n =6) and cerebrospinal fluid (dose 0.5 mg, n =12) there were no measurable amounts of DHE after a single i.v. dose. The 32-h cumulative urinary excretion was 0.02-0.04% of the 1.0 mg intravenous dose. In one subject renal (0.18 ml/min) and extrarenal (692.9 ml/min) clearance of DHE was calculated. According to our results DHe is probably eliminated mainly by hepatic metabolism. The pharmacokinetic properties of DHE indicate a fast clinical response without a cumulative action.

Adult↗

The effect of intravenously administered Palerol and Litalgin on the contraction of the human gallbladder.

One ampule of Palerol and one of Litalgin (combination preparations with vagolytic, smooth-muscle relaxing, and analgesic effects) were injected intravenously in a double-blind study in random order to 19 patients having a routine oral cholecystography. Palerol had a significant dilatation effect on the smooth muscle of the contracted gallbladder, but Litalgin only prevented further contraction caused by fatty meals. Side effects were minimal. Palerol seems to be useful in acute gallstone attacks.

Adult↗

Aminophylline in ureterolithiasis: preliminary report.

Aminophylline (3 mg/kg i.v.) was injected in six patients with colicky pain caused by a ureter stone. In all but one this theophylline derivative caused a prompt and subjectively clear decrease in pain lasting from 30 min to 2 h. Serum levels over 12 microgram/ml were associated with good pain relief. A controlled study with an intravenous aminophylline infusion is warranted, because the pain-decreasing effect was too short-lasting after a single injection.

Adult↗

Clinical pharmacokinetics of methylergometrine (methylergonovine).

Pharmacokinetic studies carried out on methylergometrine (methylergonovine) by a radioimmunoassay are reviewed. After intravenous injection the half-life of the distribution phase was only 1-3 min, explaining the fast and strong oxytocic response in puerperal mothers. The fast tissue uptake was also obtained in the rabbit uterus in situ with a steep dose-response curve. The rate of gastrointestinal absorption appeared to be slower in patients during puerperium (Tmax 3 h) in comparison with healthy male volunteers (Tmax 0.5 h). The bioavailability after administration was about 60%. After intramuscular injection the rate of absorption was rapid (Tmax 0.5 h). The short half-life of the elimination phase (about 0.5-2 h), low apparent volume of distribution (about that of extracellular water of the body), and the relatively high total plasma clearance value (about 120-240 ml/min) were direct evidence of the rapid elimination of the drug from the body. After repeated oral administrations no accumulation was found. Only about 3% of the single oral dose was excreted into urine, indicating hepatic metabolism and elimination. Although methylergometrine had a good penetration into breast milk in dogs, in postpartum women the mild concentrations were hardly measurable and clinically nonsignificant. Apparently there is no correlation between the plasma level and clinical effect of methylergometrine.

Animals↗

Transfer of free and conjugated oxazepam across the human placenta.

Six women, 13 to 16 weeks pregnant, and 12 women at 38 to 40 weeks gestation, received oral oxazepam about 12 h before legal abortion, by hysterotomy in the former and before elective caesarean section in the latter group. The concentrations of free and conjugated oxazepam in maternal and fetal plasma were determined by gas-liquid chromatography. In early pregnancy the mean ratio between the plasma concentration of total (free + conjugated) drug in the umbilical cord and a maternal vein was 0.6 whereas in late preganancy the ratio vein was 1.1. Both in early and late pregnancy, the free and glucuronide conjugate of oxazepam were found in the fetus at concentrations which indicated transplacental passage of the parent drug and its metabolite. There was great interindividual variation in the plasma levels both of free and conjugated oxazepam.

Adult↗

Comparative study of the clinical effects of tofizopam, nitrazepam and placebo as oral premedication.

In a double-blind randomized study 47 patients received tofizopam 100 mg orally the night before operation, and 100 mg on the morning of operation; 49 patients received nitrazepam 5 mg and 50 patients received placebo. On average the nitrazepam group slept better and were better sedated than the tofizopam or placebo groups. Compared with placebo or nitrazepam, tofizopam decreased the excitement of the patients. The effect tofizopam on apprehension and excitement was significantly better than those of placebo or nitrazepam. Nitrazepam, but not tofizopam, significantly decreased the induction requirements of thiopentone.

Administration, Oral↗

Plasma concentrations of lidocaine (lignocaine) after cranial subcutaneous injection during neurosurgical operations.

After cranial subcutaneous injection of lidocaine 0.8-3.7 mg/kg+adrenaline (epinephrine) 1:200,000 in neurosurgical patients, fast drug absorption was found with peak plasma concentrations of 0.6-1 microgram/ml in 5-10 min. However, the concentrations remained above the lowest effective antiarrhythmic level of 0.6 microgram/ml for only about 10 min. In one patient, simultaneously administered intravenous lidocaine had an additive effect on those levels. Induced hypotension (sodium nitroprusside) during aneurysm operations decreased the arterial plasma level of lidocaine and was followed by a new peak after discontinuation. Thus the absorption of a drug during induced hypotension from subcutaneous tissue is often erratic.

Adult↗

Radioimmunoassay for atropine and l-hyoscyamine.

A simple, specific and sensitive radioimmunoassay is described for atropine (dl-hyoscyamine) and l-hyoscyamine. Antiserum was obtained from rabbits immunized with an immunogen prepared by coupling l-hyoscyamine to human serum albumin. By using 3H-atropine as tracer, the assay can detect atropine and l-hyoscyamine concentratins down to 9 nmol/l(2.5 ng/ml) in a 0.1 ml serum or plasma sample. The recovery of atropine was near 100% when the drug was added at different concentrations to normal, pooled human plasma. Atropine and l-hyoscyamine are recognized equally well by the antibodies, but some other structurally related drugs (homatropine scopolamine) and atropine hydrolysis products (tropine, tropic acid) do not interfere. The usefulness of the method in pharmacokinetic studies was shown by assaying atropine concentrations in serial serum samples from two patients, who were given 1.3 mg atropine on connection with anaesthesia. A biexponential serum decay curve was demonstrated in both cases with a very rapid distribution phase (t 1/2 0.63 and 1.38 min.) and a much slower elimination phase (t 1/2 1.86 and 2.09 hrs.).

Adult↗

Transfer of lorazepam and its conjugate across the human placenta.

The concentrations of lorazepam and its conjugate were determined in maternal venous serum, in umbilical vein and artery serum, and in amniotic fluid after a single 2 mg intramuscular and 2.5 mg oral maternal administration. During normal delivery (2 mg intramuscular injection) and caesarean section (2.5 mg orally) both the unconjugated and conjugated forms of lorazepam were found in the umbilical circulation and amniotic fluid. The serum protein unbound fraction was 14.0 +/- 4.8 (S.D.) % in maternal circulation and 20.8 +/- 3.1% in umbilical circulation. Generally, lorazepam was a useful anxiolytic agent during normal delivery and as a sedative on the night before caesarean section.

Adult↗