Rapid high-performance liquid chromatographic assay of cinnarizine in human plasma.
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Chromatography, High Pressure Liquid↗
Biomedical subjects
V Nitsche
Publications and source records attributed to V Nitsche.
Serum levels of 8-methoxypsoralen in two different drug preparations: correlation with photosensitivity and UV-A dose requirements for photochemotherapy.
In a quantitative study we have compared the serum levels, the time course and the photosensitizing capacity of a conventional crystalline 8-methoxypsoralen brand and an investigational liquid formula. Evidence is presented showing that the liquid preparation is superior to the crystalline form: it peaks earlier after ingestion, it produces higher and more constant degree of photosensitization, it is eliminated more rapidly from the blood, and it requires a lower UV-A dose for eliciting photosensitivity reactions aiming at a reduction of the total cumulative UV-A dose required for clearing psoriasis.
Adult↗
The pharmacokinetics of valproic acid after oral and parenteral administration in healthy volunteers.
The pharmacokinetics of valproic acid were investigated in six healthy volunteers. After a single intravenous dose of 1,000 mg valproic acid, the pharmacokinetic parameters were determined according to the open two-compartment model. Bioavailability of valproic acid was performed comparing the areas under curves (AUC) after i.v and an equal single oral dose. The half-life of the initial phase was t 1/2 alpha = 0.64 +/- 0.32 h, and the elimination half-life was calculated as t 1/2 beta = 11.55 +/- 2.33 h. The distribution volume of the central compartment was Vc = 9.9 +/- 0.78 L, the apparent volume of distribution was Vd beta = 18.2 +/- 6.2 L, and the distribution volume at steady state was Vss = 12.6 +/- 1.2 L. The value for the average total clearance was Cltot = 51.1 +/- 11.9 ml/min. The study showed that in comparison to single dosing, the elimination half-life increased in average for four hours after multiple dosing (p less than or equal to 0.05). There was only a poor correlation between serum concentrations and concentration of valproic acid in saliva (r = 0.42).
Administration, Oral↗
[5-Methoxypsoralen: bioavailability and pharmacokinetics].
The bioavailability of two galenic formulations of 5-methoxypsoralen (5-MOP) is described. A suspension in soft gelatine capsules was tested against a micronized powder in hard gelatine capsules on six volunteers, both in a dosage of 40 mg. The comparison of the AUC shows a significant better availability of the suspension (p less than or equal to 0.05). The detection limit of 5-MOP is 2 ng/ml plasma. The described analytical method is accurate and rapid--recovery near 100%--and is suitable for routine analysis. The pharmacokinetic parameters for 5-MOP are 2.3 h for the elimination half-life and 0.344 h-1 for the elimination rate constant.
5-Methoxypsoralen↗
[Therapeutic efficacy of slow-release allopurinol in gout and hyperuricaemia (author's transl)].
The efficacy of a retard preparation of allopurinol is verified by biochemical, pharmacological and clinical investigations. The action of a 300 mg allopurinol tablet, with normal release and absorption parameters, is based on the specific activity of oxypurinol, a metabolite which is formed from allopurinol according to a biotransformation process. The inhibitory action of oxypurinol on xanthine oxidase amounts to only 1/5th of that of allopurinol. On the other hand allopurinol shows an extremely short half life, so that a slow-release preparation of allopurinol seems the better way of administration to get adequate uricostatic efficacy by a single dose over a 24-hour period.
Allopurinol↗
[8-Methoxypsoralen (8-MOP)-a new galenic form and its relation to 8-MOP serum levels (author's transl)].
A bioequivalence study was performed with two different 8-MOP preparations. Thirty-eight patients participated in the investigation. We compared a product already marketed containing a micronized powder in hard gelatine capsules with a new product in soft gelatine capsules containing the 8-MOP in a solution. With the new galenic preparation the serum level obtained was 3.2 (P less than or equal to 0.01) times higher than with the old product. Thus, the improved resorption out of the solution was mainly responsible for these results.
Dosage Forms↗
[Diphenylhydantoin intoxication following the exchange of seemingly equal DPH-preparations (author's transl)].
Following replacement of diphenylhydantoin (DPH) medication by a DPH preparation of different manufacture in a 41 years old woman the patient developed in spite of identical dosage clinical symptoms of overdosage which could be confirmed by EEG and determination of serum levels. In healthy volunteers the serum levels after a single oral dose of 300 mg of Epilan D Gerot and Difhydan respectively were compared. Although both preparations contained the acid of DPH significant differences in serum levels were observed. Therefore it must be concluded that the extent of the resorption differs greatly and that galenics plays a major role with regard to the bio-availability of the drug. From this single dose study no conclusions can be drawn, however, to the serum levels in long term therapy. The early clinical manifestations as well as the value of EEG and plasma level determinations in recognition of an overdosage during DPH therapy are discussed.
Adult↗
[Determination of benzbromarone in serum following combined therapy with allopurinol and benzbromarone (author's transl)].
A rapid method is described for benzbromarone assay in human serum. Protein precipitation is followed by extraction of the active substance. After centrifugation the clear organic layer is evaporated to dryness, redissolved in methanol and injected on a HPLC-column. Detection limits for this method of assay are 0.1 microgram benzbromarone/ml serum. The blood level for therapeutic concentrations lies between 1 and 2.5 microgram/ml. Some pharmacokinetic data were presented. The half-life of benzbromarone is 2.6 h.
Adult↗
[Anticonvulsive combined therapy (author's transl)].
19 patients were treated with valproic acid (VPR) in combination with classical anticonvulsants (phenytoin, phenobarbitone, primidone, carbamazepine). Patients with a mean serum concentration of 340 micron moles/l showed a marked improvement as to the frequency of seizures or were even completely free from seizures, provided that the other anticonvulsants were also given in the therapeutic range. Cases showing only a slight reduction in seizure frequency or no improvement had a mean serum level of 229 micron moles/l. This investigation shows that in severe cases of epilepsy treated by combined therapy all given anticonvulsants must reach therapeutic levels to achieve effective control of seizures in most patients.
Anticonvulsants↗
[A new and quick method for determination of allopurinol and oxipurinol in serum (author's transl)].
A method is described for allopurinol and oxipurinol assay in human serum for concentrations reached after usual therapy. The HPLC-method is based on a quick preparation of the serum samples including protein precipitation, evaporation to dryness, dissolving of the residue in citric acid and injecting the final solution on to the HPLC column. Detection limits for allopurinol are 0.05 microgram/ml serum and for oxipurinol 0.2 microgram/ml serum.
Allopurinol↗
[Administration of anxiolit retard before strumectomy (author's transl)].
With the aid of v. Zerssen's emotional scores the emotional condition of patients with toxic or cold thyroid adenomas was tested before operation with and without administration of oxazepam (Anxiolit retard). There was a significant improvement of the general condition not only in patients with toxic adenoma but also in patients with cold adenoma. Thus the preoperative application of Oxazepam is indicated before strumectomy to avoid stress symptoms and anxiety fits.
Adenoma↗
[Radiosensitization with metronidazole. Pharmacocinetical comparison by means of blood level curves after administration of "metronidazol" in the form of tablets, suppositories, and enemas (author's transl)].
Severe acute gastrointestinal side-effects following high oral doses of metronidazole (6 g/m2) could be avoided by a combined oral and rectal application. With tablets and an enema (1 g metronidazole/2 ml) in a ratio 1:4 and an increased dosage of 10 g/m2, maximal serum concentrations of about 200 micrograms/ml are obtained like after an oral dosage of 6 g/m2. The maximal radiosensitizing effect on hypoxic tumor cells is seen five hours after oral application and seven hours after the combined oro-rectal application. No longterm toxicity was found following six high doses of metronidazole.
Administration, Oral↗
[Assessment of psychoactivity and long-term efficacy of a retard preparation of oxazepam by blood level determinations and quantitative eeg and psychometric analyses (author's transl)].
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Adult↗
Initial clinical experience with the radiosensitizing nitroimidazole Ro 07-0582.
The 2-nitroimidazole derivate Ro 07-0582 is known from experimental studies to be a very efficient radiosensitizer of hypoxic cells. Experiences with its clinical use are very limited so far. This study reports the side effects observed in the use of this drug in 12 patients. Nine of these patients were suffering from brain tumors, 3 from extracerebral tumors. In 8 of our 12 patients a sensoric polyneuropathy occurred which was strongly related to the total dose of the drug administered. Polyneuropathy was observed on the average after a total dose of 26 grams, but was already noticed at doses as low as 22 grams. It showed a good tendency for remission after termination of the drug treatment and was reversible in all patients within 4 weeks. In one patient with a brain tumor a severe organic psychosyndrome occurred which is possibly related to the drug. This side effect was also reversible. In this small group of patients the critical dose limit seems to be 29 grams. This dose can be divided into 6 fractions of 60-80 mg/kg. Up to the present knowledge this single dose is likely to give an enhancement ratio of 1,5, which would be extremly valuable for the treatment of hypoxic tumor cells.
Adolescent↗
Oral bioavailability of atenolol.
The bioavailability of two formulations of atenolol was compared in an open, randomized crossover study. Each film-coated tablet contained 100 mg of active drug. The plasma concentrations of atenolol were determined using a newly developed and specific high-performance liquid chromatography procedure. The areas under the concentration-time curves (AUC) were calculated, as were pair differences and ratios for individual AUC values and for maximum plasma levels. The latter were determined (Cmax.(m] and calculated (Cmax.(c] at the corresponding time values (tmax.) for test and reference formulations, and were then tested for statistical significance. The 95% confidence limits for both test and reference preparations, taken according to Westlake or Wilcoxon, were found to be 80.0-114.7% for AUC, 80.2-119.9% for Cmax. and 74.5-132.8% for tmax. In terms of pharmacokinetic target criteria, therefore, it can be seen that there were no substantial differences between the two film-coated tablets. The two atenolol preparations, therefore, may be classified as bioequivalent.
Administration, Oral↗