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S Symchowicz

Publications and source records attributed to S Symchowicz.

At least 37 records · Page 2Linked to original sources
PubMed1984

Quazepam kinetics in the elderly.

The kinetics of quazepam, a benzodiazepine hypnotic, was studied in 10 geriatric subjects. Each received one 15-mg tablet of quazepam. Blood samples were collected before and at specified times (up to 672 hr) after dosing. Plasma concentrations of quazepam and its two major active plasma metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam), were determined by specific GLC methods. Kinetics were best described by a two-compartment open model with first-order absorption/formation kinetics and standard equations. Quazepam was rapidly absorbed, with a t1/2 of 0.8 hr. The mean maximum plasma level (Cmax) was 29.3 ng/ml. The disposition t1/2s in the distribution (t1/2 alpha) and elimination (t1/2 beta) phases were 3.5 and 53.3 hr. 2-Oxoquazepam was rapidly formed with quazepam, with an apparent formation t1/2 of 0.8 hr. Mean Cmax was 14.5 ng/ml. The t1/2 alpha and t1/2 beta of 2-oxoquazepam were 4.2 and 43.1 hr, of the order of those of quazepam. The t1/2 beta of N-desalkyl-2-oxoquazepam, formed from 2-oxoquazepam, was 189.7 hr, much longer than that of its precursor. Comparison of these data with reported kinetic data in young subjects shows that t 1/2 betas of quazepam and 2-oxoquazepam increased only slightly or not at all with age, but that the t 1/2 beta of N-desalkyl-2-oxoquazepam in the elderly was more than twice that in young subjects.

Absorption↗
PubMed1984

Multiple-dose quazepam kinetics.

Quazepam, a benzodiazepine hypnotic, was studied in normal subjects to evaluate steady-state kinetics of quazepam and of its major active plasma metabolites, 2-oxoquazepam and N-desalkyl-2-oxoquazepam, after 15 mg once daily by mouth for 14 days. The kinetics of quazepam and 2-oxoquazepam can be best described by a two-compartment open model with first-order absorption/formation kinetics. Quazepam was rapidly absorbed and its two major plasma metabolites appeared very quickly in systemic circulation. The elimination t 1/2s of quazepam, 2-oxoquazepam, and N-desalkyl-2-oxoquazepam were 41, 43, and 75 hr. Steady-state levels were predictable from the kinetic data and were reached by the seventh dose for quazepam and 2-oxoquazepam and by the thirteenth dose for N-desalkyl-2-oxoquazepam. These kinetic profiles may explain the clinical hypnotic effect of quazepam--rapid induction of sleep and long duration of clinical action without appreciable rebound insomnia.

Absorption↗
PubMed1984

Comparative pharmacokinetics of Sch 28191 and amphotericin B in mice, rats, dogs, and cynomolgus monkeys.

The pharmacokinetics of Sch 28191, the N-D-ornithyl methyl ester of amphotericin B, and amphotericin B were studied in mice, rats, dogs, and cynomolgus monkeys after an intravenous dose of 0.6 mg/kg was administered. The decline in the concentrations of Sch 28191 and amphotericin B in serum appeared to be biphasic in nature. The half-life at the distribution phase and the half-life at the elimination phase of Sch 28191 were similar to those of amphotericin B in all animals studied. The half-life at the distribution phase in serum was 0.9 to 1.5 h in all animals studied. The half-lives at the elimination phase in serum were 25 to 28 h in mice, 16 to 18 h in rats, 44 to 47 h in dogs, and 35 h in cynomolgus monkeys. The areas under the serum concentration-time curves of Sch 28191 were five- to eightfold larger than those of amphotericin B in rats, dogs, and cynomolgus monkeys but were only slightly larger than those of amphotericin B in mice. In dogs, the urinary excretion (over 9 days) of unchanged drug accounted for 23% of the Sch 28191 dose and 25% of the amphotericin B dose. The concentrations of Sch 28191 in serum were also studied after the intravenous administration of 0.3, 0.6, or 1.25 mg/kg to dogs. The serum concentration-time curves were parallel for these doses. There was a linear relationship between the areas under the concentration-time curves and the doses, indicating dose proportionality.

Amphotericin B↗
PubMed1984

Pharmacokinetics and metabolism of rosaramicin in humans.

The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t1/2S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (infinity) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces.

Administration, Oral↗
PubMed1982

Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs.

The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model. The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin. The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57). These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin.

Aminoglycosides↗
PubMed1982

Bioavailability of d-pseudoephedrine and azatadine from a repeat action tablet formulation.

The objective of this study was to compare in man the bioavailability of d-pseudoephedrine and azatadine from a repeat action tablet formulation and from conventional tablets. The repeat action tablet, containing 1 mg of azatadine maleate in the coat, and 60 mg of d-pseudoephedrine sulfate in both the coat and the core, was given at 0 hour. A conventional tablet of 60 mg of d-pseudoephedrine sulfate was given at 0 and 4 hours and a conventional tablet of 1 mg of azatadine maleate was given at 0 hour. The plasma levels of d-pseudoephedrine were measured by gas-liquid chromatography and the amount of azatadine in the urine was determined by a mass fragmentographic procedure. The results showed that there were no statistically significant differences in the measured bioavailability parameters (area under plasma concentrations-time curve, maximum plasma concentration and time to reach maximum plasma concentration) for pseudoephedrine from repeat action tablets and conventional d-pseudoephedrine sulfate tablets; neither was there any statistically significant difference in the cumulative urinary excretion of azatadine from the repeat action tablets and conventional azatadine maleate tablets (p less than 0.10). These data clearly demonstrate the bioequivalence of the repeat action tablets and the conventional tablets of d-pseudoephedrine and azatadine.

Adolescent↗
PubMed1982

Comparative bioavailability of d-pseudoephedrine from a conventional d-pseudoephedrine sulfate tablet and from a repeat action tablet.

The bioavailability of a single dose of d-pseudoephedrine sulfate administered to male volunteers in repeat action tablet form (60 mg d-pseudoephedrine sulfate in the coat and 60 mg d-pseudoephedrine sulfate in the core) was compared with the bioavailability of an equivalent quantity of the drug given as two 60 mg conventional tablets, one given at 0 hour and the second 6 hours later. There was no significant difference (P less than 0.10) between the conventional tablets and the repeat action tablet formulation in area under the plasma concentration-time curve and the maximum plasma concentration of d-pseudoephedrine. Based on the data, we conclude that the repeat action tablet formulation and the conventional tablet are bioequivalent.

Adolescent↗
PubMed1982

Comparative bioavailability of a microsize and ultramicrosize griseofulvin formulation in man.

The bioavailability of 500 mg of a microsize formulation of griseofulvin has been compared to two new ultramicrosize griseofulvin formulations, two 165 mg tablets and a 330 mg tablet, in sixteen healthy, male, volunteers in a randomized crossover study design. Based on the griseofulvin plasma levels measured at specified times over a 48-hour period, the major bioavailability parameters (i.e., area under plasma concentration-time curve, maximum plasma concentration, and time to reach maximum plasma concentration) were determined and statistically evaluated. The results showed that one 330 mg ultramicrosize tablet is bioequivalent to two 165 mg ultramicrosize griseofulvin tablets and that either ultramicrosize griseofulvin dosage regimen is bioequivalent to 500 mg of the microsize griseofulvin formulation.

Biological Availability↗
PubMed1981

Bioavailability of orally administered propiram fumarate in humans.

Propiram bioavailability was determined in 10 healthy volunteers after a single role administration of 50 mg (base equivalent) of propiram fumarate in tablet or solution dosage from in a randomized crossover design. The plasma drug concentration-time curve revealed a one-compartment open model with first-order absorption kinetics. There were no statistically significant differences (P greater than 0.05) between all of the measured pharmacokinetic parameters obtained from the tablet and the solution with the exception of the absorption lag time (tlag), where the tablet had a significantly longer tlag. The drug given as a tablet or solution was absorbed rapidly after oral administration with an apparent absorption rate constant of 3.7 hr-1 for both dosage forms. The Cmax value (308 ng/ml for the tablet and 342 ng/ml for the solution) was attained at approximately 1 hr after oral administration. The elimination half-life was 5.2 hr for the tablet and 4.4 hr for the solution, and the apparent distribution volume was 2.31 liters/kg for the tablet and 1.94 liters/kg for the solution. Total body clearance was much greater than renal clearance, indicating extensive metabolic clearance for both dosage forms. The study showed that propiram administered as the tablet was bioequivalent to the solution.

Adult↗
PubMed1981

Pharmacokinetic study of sisomicin in humans.

Detailed analyses of the pharmacokinetics of sisomicin administered at doses of 25, 50 and 100 mg intravenously and intramuscularly to healthy volunteers established that the drug is handled by a two-compartment open model system with a disposition (elimination) half-life of 2.6 hr. The kinetic estimates over this dose range are linear and independent of dose and were verified by a 60-min infusion experiment in which dose and the maximum serum concentration achieved (5 microgram/ml) were predicted correctly. Sisomicin was rapidly distributed to the tissue compartment, and equilibrium between the central and the tissue compartment was established by 30 min after dosing. Renal clearance (55 ml/min) of sisomicin was about 30% less than total body clearance (78 ml/min). Total urinary excretion of sisomicin during a 24-hr period following drug administration was about 70% of the dose. The disposition kinetics of sisomicin following intramuscular administration are similar to those obtained following rapid intravenous administration. Intramuscular bioavailability of sisomicin for the doses of 25, 50, and 100 mg was greater than 95%. Based on these results, various initial loading infusion doses and maintenance infusion rates were calculated to provide specific desired peak and steady-state serum sisomicin concentrations rapidly. The purpose was not to expose patients to potentially toxic high peak concentrations of drug while maintaining these concentrations during the current therapeutic dosing intervals of 8 to 12 hr.

Biological Availability↗
PubMed1980

Comparison of netilmicin and gentamicin pharmacokinetics in humans.

In a crossover study, single doses of netilmicin and gentamicin were administered intramuscularly, each at 1.0 and 2.5 mg/kg. The serum concentrations, analyzed by a two-compartment open model with a first-order absorption, indicated that the pharmacokinetics of the drugs are essentially the same. Both drugs were rapidly absorbed and distributed after administration. No significant differences were observed between the two drugs in disposition half-life, rate of distribution and elimination, area under the serum concentration-time curve, urinary excretion, total body clearance, and renal clearance. After 1.0 mg/kg, the maximum serum concentration of netilmicin (5.18 microgram/ml) was only slightly lower than that for gentamicin (5.76 microgram/ml), but no difference was found after the 2.5-mg/kg dose.

Adolescent↗
PubMed1980

High-pressure liquid chromatographic method for determination of rosaramicin in humans.

A high-pressure liquid chromatographic method has been developed for the quantitative determination of rosaramicin in serum. This procedure involves addition of an internal standard, adjustment to alkaline pH, treatment with potassium carbonate, ether extraction, and a reverse-phase column separation with acetonitrile-acetate buffer mixture as the mobile phase. This technique produces a good linear relationship between the peak height ratio and the rosaramicin concentration. In addition, this method has proven to be quite specific for rosaramicin, since many of its derivatives tested do not interfere with the assay. The method is accurate and reproducible with a sensitivity of about 0.01 microgram of rosaramicin per ml of serum. It may be useful in monitoring drug levels in serum of patients and also for the pharmacokinetic studies of the drug in humans.

Chromatography, High Pressure Liquid↗
PubMed1977

Effect of dexamethasone on monoamine oxidase inhibiton by iproniazid in rat brain.

Chronic (6 days) dexamethasone administration caused a slight decrease of rat brain MAO enzyme activity which was reflected by lower levels of 14C-homovanillic acid (HVA) and increased levels of 14C-3-methoxytyramine (3MT) following intracisternal injections of 14C-dopamine (DA). Opposite results with dexamethasone were obtained in iproniazid (MAO-inhibited)-treated rats. In these animals, brain MAO enzyme activity was significantly increased by dexamethasone. This effect increased with the duration of dexamethasone treatment and appeared to be dose dependent. In the brain areas tested (hypothalamus, midbrain, cerebellum, pons and medulla, olfactory, rest of brain) increases of MAO enzyme activity were also indicated by lower levels of 14C-3MT and increased levels of 14C-HVA formed from intracisternally injected radiolabeled DA. Treatment with other glucocorticoids (16alpha-methyldichlorisone, 16beta-methylprednisone and prednisolone) had a similar effect on 14C-DA metabolism. On the other hand, desoxycorticosterone, progestone, estradiol and testosterone, did not exhibit this property. The data indicate that chronic glucocorticoid treatment may have a slight inhibitory effect on brain MAO and also has the ability to partially reverse or antagonize the inhibition of MAO caused by iproniazid.

Animals↗
PubMed1975

Maternal and fetal hemodynamic effects of diazoxide.

Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.

Animals↗