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Biomedical subjects

H Roseboom

Publications and source records attributed to H Roseboom.

13 recordsLinked to original sources
PubMed1990

Pharmacokinetics of eltoprazine in healthy male subjects after single dose oral and intravenous administration.

The kinetics, safety and tolerability of eltoprazine hydrochloride were studied in an open, cross-over, partially randomised design after single oral (8 mg) and intravenous (3 and 8 mg) doses to 12 healthy male subjects. After intravenous administration, the mean t1/2 ranged from 7 to 9 h, the MRT was 11 h, CL was 487 +/- 148 (3 mg dose) and 471 +/- 56 (8 mg dose) ml kg-1 h-1, while CLR was 226 +/- 124 (3 mg dose) and 189 +/- 38 (8 mg dose) ml kg-1 h-1. The Vss was 3.3 +/- 0.7 (3 mg dose) and 3.8 +/- 0.5 (8 mg dose) 1 kg-1. Cumulative renal excretion was 40%. The AUC and the cumulative urinary excretion were directly proportional to dose within the range of 3-8 mg. Values of tmax varied from 1 to 4 h after oral administration. The mean Cmax value was 24 ng ml-1 after an oral dose of 8 mg. The plasma elimination half-life after oral administration was 9.8 +/- 3.9 h. Absolute oral bioavailability was 110 +/- 32%. Dose-dependent somnolence was observed.

Administration, Oral↗
PubMed1983

Gas chromatographic alkylation studies of phenytoin, mephenytoin and primidone: investigation of butylated derivatives.

The alkylation of phenytoin, mephenytoin and primidone with n-alkyl iodides in N,N-dimethylacetamide with tetramethylammonium hydroxide was investigated by gas chromatography. With methyl iodide phenytoin and mephenytoin were each converted into a single derivative; the use of other alkyl iodides yielded more than one product. Primidone was converted with methyl iodide and butyl iodide into a major derivative (> 90%) and a minor one. Butylation of the compounds by this method was compared with butylation in an acetone-butyl iodide mixture with potassium carbonate, caesium carbonate or silver oxide added, and with on-column butylation. All these methods resulted in the production of more than one derivative. The derivatives were identified by mass spectrometry and by 1H NMR and 13C NMR. With the acetone-butyl iodide-silver oxide method the main derivatives were O-butylated compounds. The other methods yielded predominantly N-butylated derivatives.

Journal Article↗
PubMed1979

Rapid and simple clean-up and derivatization procedure for the gas chromatographic determination of acidic drugs in plasma.

A rapid and simple clean-up and derivatization procedure that can be generally applied to the gas chromatographic (GC) determination of acidic drugs of various chemical and therapeutic classes is described. The drugs are extracted from acidified plasma with chloroform containing 5% of isopropanol, which is then evaporated. The residue is dissolved in toluene, then the drugs are back-extracted into a small volume of a methanolic tetramethylammonium hydroxide solution. The solution obtained is added to N,N-dimethylacetamide and the drugs are treated with n-butyl iodide and chromatographed as their n-butyl esters. Retention times are given for three different columns; the results show that in all but three instances one derivative is formed. The recoveries in the extraction steps were determined by GC and UV spectrophotometry. The recovery of the back-extraction and of the extraction from plasma with chloroform-isopropanol is fairly good. For some drugs toluene can be used as the extraction solvent, which has the advantage that no evaporation of the extract is necessary, and it can be extracted directly with the tetramethylammonium hydroxide solution. Chromatograms of blank plasma treated according to the described procedure do not show interfering peaks from endogenous compounds. The advantages of the proposed method are as follows. It is a standard procedure that can be used for different types of drugs, using one standard column, with no interference from endogenous compounds. Separation is achieved between drugs that differ only in the number or position of the methyl groups and between a drug and its demethylated metabolite(s). No decomposition of the products occurs during the alkylation process and injection of the resulting neutral solution is not detrimental to the column material.

Acids↗
PubMed1979

Determination of valproic acid (di-N-propyl acetic acid) in plasma by gas-liquid chromatography with pre-column butylation.

A gas-liquid chromatographic procedure for the determination of the anti-convulsant drug valproic acid in plasma or serum is described. Valproic acid is extracted from acidified plasma (or serum) into toluene containing octanoic acid as the internal standard. The toluene layer is back extracted with a methanolic solution of tetramethylammonium hydroxide; an aliquot of the methanolic layer is mixed after phase separation with N,N-dimethylacetamide and 1-iodobutane. After centrifugation the clear supernatant (which is stable for at least 24 h) is analysed by gas-liquid chromatography, on a 3% OV17 column. The procedure is rapid and sensitive, and the back-extraction step with methanolic tetramethylammonium hydroxide results in clean chromatogram obtained from blank plasma. Sample volumes of 50 microliter suffice for the determination of therapeutic levels of VPA.

Butanes↗
PubMed1979

Stability of 10-acetylphenothiazine.

The degradation kinetics of 10-acetylphenothiazine were studied after isolation and identification of its degradation products, phenothiazine, phenothiazine-5-oxide, 3H-phenothiazine-3-one, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one. The acetyl group was not present in any degradation product. The degradation rate was independent of oxygen but highly pH dependent, indicating a specific hydrogen-ion-catalyzed hydrolysis of 10-acetylphenothiazine to give phenothiazine, which was oxidized. The experimental values for the phenothiazine concentration were in good agreement with values calculated on the basis of this assumption, both in the presence and absence of oxygen.

Acetylation↗
PubMed1978

Stability of tetrahydrocannabinols II.

The biphasic degradation of delta9-tetrahydrocannabinol (I), as monitored by flame-ionization GLC, produced delta8-tetrahydrocannabinol (II), cannabidiol (X), 9-hydroxyhexahydrocannabinol (VI), 9,10-dihydro-9-hydroxyisocannabidiol (VI), and and 6,12-dihydro-6-hydroxycannabidiol (VIII) in acidic solutions. Further identification was made by GLC, mass spectrometry, and comparison with authentic samples. Only II and IV were produced above pH 4 in the neutral region by first-order kinetics. The acidic degradation of cannabidiol (X) gave I and the products of the acidic degradation of I. The initial phase of acidic I degradation was assigned to the development of solvolytic equilibria among I, VIII, X, and, possibly, isocannabidiol (IX), with the concomitant production of II and IV. Compounds VIII, IX, and X did not appear in the neutral region since ether cleavage occurred only in strong mineral acids. Hydration of the delta9-double bond resulted only in acid-catalyzed equilibria of cleaved ethers with the delta8-configurations and characterized the second phase of acid degradation of I. Cannabinol and hexahydrocannabinol were found together in several cases due to the disproportionation of I as catalyzed by silicic acid, silica gel, and chloroform.

Chemical Phenomena↗
PubMed1978

Pharmacokinetics of papaverine hydrochloride and the biopharmaceutics of its oral dosage forms.

The pharmacokinetics of completely metabolized papaverine hydrochloride were characterized by a linear sum of three exponentials on intravenous administration with respective 1.5, 19 and 107 min apparent half lives. There was a time-dependent partition from plasma water into red blood cells with an apparent half life of 1.5--3 min. The partition coefficient normally ranged between 8 and 15 at therapeutic levels but approached unity at high plasma concentrations to indicate a saturable partition. Apparent compartmental volumes of distribution referenced to total concentrations in the plasma were 4.3--4.8, 11--13 and 20--25 liters. Protein binding was 91--95%. The hepatic clearance of blood was 960 ml/min, corresponding to a hepatic efficiency of 69%, and indicated that the clearance of protein-bound drug was consistent with the observed first pass metabolism of 70% for oral solutions. No dose dependency was observed on intravenous administration or on oral administration of solutions and tablets. Tablets with release lag times of 10--15 min showed relative bioavailabilities of 52%. Two different lots of sustained release capsules showed 68 and 89% relative bioavailabilities. Release lag times among capsules ranged between 0 and 170 min. Loo-Riegelman calculations and analog computer fittings were consistent with a half life of absorption from oral solutions of 19 min and zero order release rates from tablets and sustained release capsules. Chronic studies of tablets q.i.d. and capsules b.i.d. confirmed lack of accumulation. An appropriately designed 300 mg sustained release capsule, b.i.d., for an arbitrary plasma level of 0.200 microgram/ml should have one tenth the release rate of the studied capsules.

Administration, Oral↗
PubMed1977

Oxidation kinetics of phenothiazine and 10-methylphenothiazine in acidic medium.

The rate of phenothiazine degradation in an acidic oxygen-saturated medium was studied. 3H-Phenothiazine-3-one and phenothiazine 5-oxide are produced by parallel reactions, and 7-(10'-phenothiazinyl)-3H-phenothiazine-3-one is produced in a more complex manner. The overall phenothiazine degradation rate appears to be pH independent up to pH 7.0. The degradation kinetics of 10-methylphenothiazine were studied after isolation and identification of its degradation products, 10-methylphenothiazine 5-oxide and 3H-phenothiazine-3-one. The main degradation product is 10-methylphenothiazine 5-oxide; but at low pH values and high temperatures, more 3H-phenothiazine-3-one is formed. The degradation rate of 10-methylphenothiazine is pH independent up to pH 7.

Drug Stability↗
PubMed1977

Mechanism for phenothiazine oxidation.

The mechanism of phenothiazine degradation was studied by following the degradation of 3,10'-diphenothiazine in ethanol-water mixtures as well as the electrochemical oxidation of phenothiazine. A mechanism, including the formation of an oxidized dimer and some polymers, is suggested.

Electrochemistry↗