PubMed Health⌕ Search

Biomedical subjects

D G Kaiser

Publications and source records attributed to D G Kaiser.

At least 19 recordsLinked to original sources
PubMed1992

The lazaroid U74006F, a 21-aminosteroid inhibitor of lipid peroxidation, attenuates myocardial injury from ischemia and reperfusion.

U74006F, a novel new 21-aminosteroid inhibitor of lipid peroxidation, has been effective in preventing free-radical-mediated injury in central nervous system models. To assess its ability to diminish myocardial injury due to ischemia and reperfusion, U74006F (n = 11) or its vehicle (n = 11) were administered intravenously to New Zealand white rabbits. After allowing for distribution, the hearts were excised and exposed to 30 min of stop-flow ischemia and 30 min of reperfusion on a nonrecirculating Langendorf apparatus. There was diminished creatine phosphokinase release; improved peak positive dP/dt, developed pressure, and peak negative dP/dt; and diminished diastolic pressure in the group treated with U74006F. Thus, pretreatment with U74006F diminished myocardial injury and enhanced systolic and diastolic functional recovery, probably by protecting the lipid component of cell membranes from peroxidation by reactive oxygen metabolites.

Animals↗
PubMed1990

The fate of soluble steroids within breast prostheses in humans.

The long-term fate of 6-alpha-methyl-methylprednisolone hemisuccinate (MPHS) placed into breast prostheses prior to implantation in humans was determined. MPHS hydrolyzes to the active form 6-alpha-methylprednisolone (MP) in water, which then diffuses out of the implant. Twenty prostheses were recovered 5.3 to 34.7 months after placement, and the solution inside was analyzed for MPHS and MP. Half-lives were calculated for the hydrolysis of MPHS to MP (3.4 +/- 0.58 months [mean +/- SEM]) and for the diffusion of MP out of the prostheses (20.63 +/- 6.10 months). The large half-lives found imply that MPHS slowly hydrolyzes to MP, and that active steroid is released for a longer time than was previously thought. This long release could be the cause of the long-term effects seen with steroids used in this manner.

Breast↗
PubMed1989

Potentiation of aspirin-induced gastric lesions by exposure to cold in rats. Role of acid secretion, mucosal blood flow, and gastric mucosal prostanoid content.

We investigated the mechanism by which exposure to cold sensitizes rats to the formation of gastric lesions after a low dose of aspirin (50 mg/kg). Six times more lesions were produced by aspirin plus cold than by aspirin alone. Three hypotheses were studied to explain the synergism of aspirin plus cold on lesion formation: gastric acid hypersecretion, reduced gastric mucosal blood flow, and decreased prostanoid synthesis by the stomach. Cold, and cold plus aspirin, stimulated gastric acid secretion (to a similar extent), whereas aspirin had no effect. Gastric mucosal blood flow, measured by the hydrogen gas clearance method, was decreased by cold, aspirin, and aspirin plus cold, and the extent of decrease was similar. Prostanoid generation [prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2] by the gastric corpus mucosa was not affected by cold, but was reduced equally (by at least 90%) in animals receiving aspirin alone or aspirin plus cold. After oral administration of aspirin, the plasma contained mostly salicylic acid (98%), whereas the gastric mucosa contained mostly aspirin (80%-85%). We conclude that the synergism of aspirin plus cold on the formation of gastric lesions probably results from the combined effects of three factors: increased secretion of acid (because of exposure to cold) that is in contact with a gastric mucosa in which blood flow is reduced (because of exposure to cold or to aspirin), and in which the synthesis of cytoprotective prostaglandins is inhibited (by aspirin). Such mucosa may be particularly vulnerable to the damaging effect of hyperacidity.

Animals↗
PubMed1989

Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans.

The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: 1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; 2) chiral inversion of R-(-)-[2H3]ibuprofen is not subject to a discernible deuterium isotope effect; and 3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence.

Adult↗
PubMed1988

Gas chromatographic determination of guanadrel in plasma and urine.

To evaluate the pharmacokinetics and drug availability from various dosage formulations, a method for the determination of guanadrel, (1,4-dioxaspiro[4,5]dec-2-ylmethyl)guanidine, in plasma and urine was required. A gas chromatographic procedure, based on formation of a hexafluoroacetylacetone derivative in a two-phase system of water and toluene, was developed. The limit of determination of the method is 5 ng/ml guanadrel in plasma and 15 ng/ml guanadrel in urine. Statistical analyses indicate average recoveries of 98.1 +/- 18.0 and 104.4 +/- 15.6% from plasma and urine, respectively. Mass spectrometric analyses, in conjunction with gas chromatography, confirmed the specificity of the method for intact drug. The procedure was applied successfully to drug absorption studies in humans.

Chemical Phenomena↗
PubMed1986

Pharmacokinetics of flurbiprofen.

Both radiolabeled and nonlabeled drug have been used to study the pharmacokinetics of flurbiprofen (Ansaid, Upjohn). Drug absorption is rapid, drug disappearance half-life is independent of oral dose, and the area under the plasma drug concentration versus time curve increases with increasing oral dose. Elimination of intact drug from the peripheral circulation is biphasic and rapid. Following a single oral dose of 100 mg of flurbiprofen, drug bioavailability is equivalent using regimens of four 25-mg tablets, two 50-mg tablets, or one 100-mg tablet once daily. Long-term administration of flurbiprofen appears neither to inhibit nor induce the drug's metabolism.

Aspirin↗
PubMed1978

Electron-capture GLC determination of ibuprofen in serum.

To evaluate drug-protein binding, a sensitive method for the determination of ibuprofen in submilliliter amounts of serum was required. A specific and highly sensitive procedure, based on benzene extraction of the acidified specimen. TLC of the benzene extract residue, fomation of the pentafluorobenzyl esters of the materials eluted from the thin-layer chromatogram, and quantification of the pentafluorobenzyl esters by GLC, was developed. Utilizing electron-capture detection, the method is sensitive to 0.1 microgram of ibuprofen/0.1 ml of serum. Statistical analyses indicated an average recovery of 97.7% with a standard deviation of +/- 7.3%. Mass spectrometric analysis, in conjunction with GLC, confirmed the specificity of the method for the intact drug. The procedure was applied successfully to drug absorption and drug-protein binding studies in humans.

Blood Proteins↗
PubMed1978

Ventilatory response to medroxyprogesterone acetate in normal subjects: time course and mechanism.

The time course of ventilatory adaptation to medroxyprogesterone acetate (MPA) and potential mediators of this response in plasma and lumbar CSF were determined in five healthy adult males. A significant decrease in arterial PCO2 (PACO2) at rest and exercise was noted within 48 h of drug administration with the maximum effect reached within 7 days and amounting to a 5-Torr decrement in PACO2. Blood and lumbar cerebrospinal fluid pH because significantly alkaline to control as soon as the ventilatory resporse was noted and remained alkaline during the treatment period. The ventilatory and dP/dt max response to exogenous CO2 was unchanged but their response to moderate exercise was increased after MPA. MPA-rlated materials were detected in both the plasma and CSF as soon as the ventilatory response was noted. The increase in CSF MPA-related materials approximated the unbound fraction determined in plasma. We conclude that [H+] in plasma and CSF is a function rather than a cause of ventilator acclimatization to MPA. MPA-related materials are capable of crossing the blood-brain barrier and could potentially exert their ventilatory stimulant effect by some central mechanism.

Adult↗
PubMed1977

Generic propoxyphene: need for clinical bioavailability evaluation.

Plasma level data on two investigational capsule formulations of propoxyphene with similar physicochemical parameters demonstrate that the formulations have different in vivo bioavailabilities. The potential bioavailability problems with water-soluble drugs and the lack of correlation of in vitro and in vivo parameters for equivalent drug formulations are discussed.

Adult↗
PubMed1976

Isomeric inversion of ibuprofen (R)-enantiomer in humans.

Enantiomeric compositions of the major urinary metabolites of ibuprofen [(RS)-2-(4-isobutylphenyl)propionic acid]were characterized after oral administration of the racemic mixture and oral administration of the individual enantiomers to normal human volunteers. Resolution of the diastereomeric amides, formed by reaction of the urinary metabolites with (S)-(-)-alpha-methylbenzylamine, was achieved by GLC. Only the (R)-(-)-enantiomer of the intact drug was inverted to its optical antipode, (S)-(+), in humans. However, both (S)-(+)- and (R)-(-)-enantiomers of the intact drug were transformed independently in vivo to the major metabolites, i.e., 2,4'-(2-hydroxy-2-methylpropyl)phenylpropionic acid and 2,4'-(2-carboxypropyl)phenylpropionic acid. In vivo metabolism of ibuprofen to its carboxy metabolite was not stereoselective.

Adult↗
PubMed1976

Fluorometric determination of trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles in biological materials.

Interest in the 5-, 6-, and 7-trifluoromethyl-substituted 2,3-bis(4-methoxyphenyl)indoles as potent, orally active anti-inflammatory agents required a method for their determination in serum, urine, and feces to permit studies of their absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific procedure was developed based on an ethyl acetate extraction of alkaline specimens and subsequent fluorometric analysis of ethanolic solutions of the extract residues. The method is sensitive to 0.1 microgram/ml, 0.5 microgram/ml, and 0.7 microgram/100 mg of these compounds in serum, urine, and feces, respectively. Overall mean recoveries and standard deviations of the 5-, 6-, and 7-trifluoromethyl-substituted compounds from biological samples were 102.2 +/- 3.0, 102.2 +/- 5.4, and 100.5 +/- 5.7%, respectively. The procedure was applied successfully to absorption studies with 2,3-bis(4-methoxyphenyl)-7-(trifluoromethyl)indole in the dog.

Animals↗
PubMed1975

GLC determination of ibuprofen [dl-2-(p-isobutylphenyl) propionic acid] enantiomers in biological specimens.

To study the behavior of the d- and l-isomers of ibuprofen in humans, a method for the determination of the individual enantiomers in plasma and urine was required. A specific procedure was developed based on (a) benzene extraction of the acidified specimens, (b) TLC of the benzene extract residue, (c) formation of the l-alpha-methylbenzylamides of the materials eluted from the chromatograms, and (d) quantification of the resulting diastereoisomeric amides by GLC in conjunction with flame-ionization detection. When using a 1-ml aliquot of the specimen, the method is sensitive to 1 mug of each enantiomer/ml of plasma or urine. As compared to simple aqueous solutions, the average recoveries of the enantiomers from plasma and urine ranged from 94 to96%. Mass spectrometric analyses, in conjunction with GLC, confirmed the specificity of the method for the intact enantiomers. The procedure was applied successfully to drug absorption studies in humans. After oral administration of the racemic mixture, the predominant enantiomer in peripheral circulation and excreted in urine was of the d-configuration.

Adult↗
PubMed1975

Fluorometric determination of 2,3-bis(p-methoxphenyl)imidazo(1,2-a)pyrimidine in biological materials.

Interest in 2,3-bis(p-methoxyphenyl)imidazo[1,2-a]-pyrimidine as a potent, orally active, anti-inflammatory agent required a method for its determination in serum, urine, and feces to permit studies of its absorption, metabolism, and excretion. A simple, rapid, sensitive, and specific procedure was developed based on an ethyl acetate extraction of alkaline specimens and subsequent fluorometric analysis of ethanolic solutions of the extract residues. The method is sensitive to 0.2 mug/ml, 0.3 mug/ml, and 1.2 mug/100 mg of drug in serum, urine, and feces, respectively. The overall mean recovery and the standard deviation from biological samples are 99.8 +/- 5.1%. The procedure has been successfully applied to absorption studies in the dog.

Animals↗