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Biomedical subjects

S Stavchansky

Publications and source records attributed to S Stavchansky.

12 recordsLinked to original sources
PubMed1992

Pharmacokinetic and metabolic disposition of p-chloro-m-xylenol (PCMX) in dogs.

The pharmacokinetic and metabolic profile of p-chloro-m-xylenol (PCMX) was studied in healthy mongrel dogs after intravenous and oral administration of single doses of 200 and 2000 mg of PCMX, respectively. Calculation of pharmacokinetic parameters was based on compartmental and noncompartmental methods. The mean pharmacokinetic parameters of elimination half-life and mean residence time were 1.84 and 1.69 hr, respectively. The apparent volume of distribution at steady state was estimated to be 22.4 liters, and the plasma clearance was 14.6 liters/hr. The bioavailability of PCMX was 21%, indicating low absorption for this drug. PCMX's metabolite data show that a presystemic elimination process (first-pass effect) is also occurring. PCMX plasma concentrations after intravenous administration of 500-, 200-, and 100-mg doses were found to be proportional to the dose given, demonstrating that the pharmacokinetic profile of PCMX is linear over the dose range studied. Biotransformation studies showed that urinary excretion was not the major route for rapid elimination of unchanged PCMX and almost all material excreted in urine was associated with the conjugated species (glucuronides and sulfates). Statistical significant differences were not found (P greater than 0.05) between the percentages excreted in urine of PCMX and its conjugated metabolites after intravenous and oral administration. The percentages excreted in urine after iv and oral doses of unchanged PCMX were, respectively, 0.45 and 0.37; total conjugates, 46.3 and 43.3; sulfates, 38.1 and 33.2; and glucuronides, 8.2 and 10.2.

Administration, Oral↗
PubMed1987

Bioequivalence and pharmacokinetic profile of promethazine hydrochloride suppositories in humans.

A bioequivalence study of promethazine hydrochloride (10-[2-(dimethylamino)propyl]-phenothiazine monohydrochloride) was conducted in 20 male human subjects with the purpose of comparing, under blind condition, the human serum levels of promethazine in three different formulations. The formulations tested were a 50-mg promethazine hydrochloride polyethylene glycol suppository, a 50-mg promethazine hydrochloride cocoa butter-white wax suppository, and a 50-mg oral dose of promethazine hydrochloride syrup. Each subject received single doses of each of the three formulations on each of three different days on a crossover basis. From the measured serum levels, estimates of the bioavailability parameters (area under the serum concentration versus time curve, time-to-peak serum concentration, and peak serum concentration) were obtained by least-squares digital computer fitting. Also, a one-compartment pharmacokinetic open model with two consecutive first-order input steps is proposed. Statistical analysis of the results was performed by using a linear multiple regression approach for the analysis of variance. No significant differences between the syrup and the polyethylene glycol suppositories were obtained (p greater than 0.05) for the above three bioavailability parameters. However, the polyethylene glycol suppositories provided statistically higher peak serum concentration, shorter time-to-peak serum concentration, and larger area under the serum concentration versus time curve than the cocoa butter-white wax suppositories.

Adult↗
PubMed1987

Effects of hypothermia on drug absorption.

The in situ rat gut technique was used to study the effects of hypothermia on the intestinal absorption of a 1 mg/ml solution of sodium pentobarbital in 0.01 M phosphate buffer (pH 6.0). Male Sprague-Dawley rats weighing between 300 and 370 g were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0-4 degrees C for 5 hr. This procedure lowers the rectal temperature of the rats from 38 to 20 degrees C. The animals were prepared for surgery using ether as anesthetic after their rectal temperature reached 20 degrees C. Water flux in and out of the intestinal lumen was estimated from tritiated polyethylene glycol 4000 concentrations in the perfusate. The disappearance rate constant of pentobarbital from the intestinal lumen was 0.0638 +/- 0.007 min-1 for hypothermic rats, in comparison to 0.114 +/- 0.0123 min-1 for normothermic rats.

Animals↗
PubMed1985

Comparison between locomotor activity changes produced by phencyclidine and D-amphetamine in CD-1 male mice.

Comparative studies were pursued to investigate the locomotor activity induced by phencyclidine hydrochloride in CD-1 male mice. Horizontal, vertical, and rotational activity counts were quantitated using an infrared beam animal activity monitor. Five doses (1.5, 2.5, 3.5, 5.0, and 10.0 mg/kg, i.p.) of phencyclidine were compared. At the 1.5 mg/kg dose, no locomotor activity changes were observed when compared to a saline control group. Increased activity was observed at the 2.5, 3.5, and 5.0 mg/kg doses. Decreased activity was observed at the 10.0 mg/kg dose when compared to the 5.0 mg/kg dose possibly due to ataxia. In addition, the locomotor activity produced by acute d-amphetamine and acute phencyclidine was compared at doses of 2.5 mg/kg and 5.0 mg/kg respectively. The overall locomotor activity levels produced by acute d-amphetamine and phencyclidine were not significantly different at p less than 0.05. The time to peak activities and peak level activities were also similar and occurred at 20-25 minutes and 1100-1300 inches respectively after i.p. administration. Administration of apomorphine after phencyclidine did not change overall locomotor activity. The data implies that phencyclidine may act primarily as a dopamine reuptake inhibitor rather than a dopamine release stimulator. Phencyclidine also affects other activity (unlike amphetamine) as seen by the severe depression of vertical activity.

Animals↗
PubMed1984

Evaluation of the bioavailability of a solid dispersion of phenytoin in polyethylene glycol 6000 and a commercial phenytoin sodium capsule in the dog.

In this study a solid dispersion of phenytoin in polyethylene glycol 6000 was prepared by the melt method. The content uniformity of the dispersion indicated a range of 98.7-102.0%. X-ray crystallographic data showed no changes in the crystalline structure of the phenytoin in the dispersion when compared with that in the bulk reagent. Scanning electron micrographs of the dispersion show a reduction in the size of the crystals when compared with the bulk reagent. The commercial product and the dispersion were compared using the USP criteria for the prompt phenytoin sodium dissolution test. The salt dissolved at a rate four times greater than the dispersion. Bioequivalency comparisons between the dispersion containing phenytoin and the commercial prompt phenytoin sodium were studied in six mixed-breed dogs. All samples were analyzed using a commercial enzyme immunoassay system. Statistical analysis of the plasma levels obtained from the animal studies indicate no significant differences (p greater than 0.05) between area under the curve, maximum plasma concentration, and time to peak for the commercial salt and the acid formulation.

Animals↗
PubMed1979

A method to predict infinity values for biexponential processes.

An equation is presented which allows infinity values for biexponential processes to be predicted in the early nonlinear phase when samples are taken at equal time intervals. This equation is independent of the value or ratio of the rate constants involved in the process. However, this method is very sensitive to noise normally associated with urine data.

Digoxin↗
PubMed1979

Solvent system effects on drug absorption.

The in situ rat gut technique was used to determine 14-C salicylic acid absorption from aqueous solutions containing 20% glycerol, 20% propylene glycol, 10% ethanol, and 20% polyethylylene glycols (PEG) 4000 and 6000. A phosphate buffer solution of salicylic acid served as a control. Observed rate constants for disappearance of activity from the gut are 0.031 min-1 for glycerol, 0.0327 min-1 for PEG 6000, 0.0395 min-1 for propylene glycol, 0.475 min-1 for polyethylene glycol 4000, 0.0558 min-1 for ethanol, and 0.0752 min-1 for the control. The rate of disappearance from the gut is significantly slower than control for 20% glycerol, PEG 4000 and PEG 6000 solutions (p less than or equal to 0.01). Activity disappears more rapidly from 10% ethanol solutions than from PEG 6000 and glycerol (p = 0.01). Water flux into and out of the intestinal lumen was estimated from tritiated inulin concentrations in the perfusate. A trend for increased loss of activity from ethanol and control solutions associated with net water efflux from the intestine was observed. These results suggest that the composition of drug delivery systems may significantly affect the absorption of drugs from solution.

Animals↗
PubMedDate not supplied

Single oral dose proportionality pharmacokinetics of almitrine bismesylate in humans.

A single-blind study was conducted in 10 healthy male subjects. Each subject was tested with four single oral doses of capsules containing 25, 50, 100, 200mg almitrine bismesylate and one dose of placebo. Blood samples were drawn as a function of time and the concentration of almitrine in plasma was determined by gas chromatography utilizing nitrogen-phosphorus detection. Linear regression analysis of the data suggested that a deviation from linearity existed between the area under the plasma concentration time curves and the dose (R = 0.96). Linear analysis of the individual data indicates that a slight negative deviation from linearity is apparent for the 200 mg dose. The same trend was observed for the mean maximum almitrine plasma concentration, Cmax, which ranged from 38.9 +/- 11.8 to 286.2 +/- 99.1 ng ml-1 for the 25 and 200 mg dose, respectively. The time to peak was relatively constant regardless of the administered dose and ranged from 2.4 +/- 0.5 h to 2.8 +/- 0.8 h. Good agreement was obtained between the observed bioavailability parameters and those predicted from the nonlinear fit of the data. Further kinetic analysis of the data revealed mean total body clearance over fraction of dose absorbed ranging from 268.2 +/- 132.8 to 436.4 +/- 191.4 ml min-1 for doses 50 and 200mg, respectively.

Administration, Oral↗
PubMedDate not supplied

Relative bioavailability of almitrine bismesylate in humans.

Bioavailability and bioequivalency studies of almitrine bismesylate from U.S. manufactured film coated, waxed, 50 mg tablets were compared in 34 normal healthy volunteers to 50 mg European film coated, waxed and unwaxed, tablets and a 0.5 per cent (w/v) oral reference solution of almitrine bismesylate in d,l malic acid. The U.S. manufactured formulations were 85.88 and 87.85 per cent of the calculated mean area under the individual concentration-time curve for almitrine bismesylate reference solution compared to 88.40 and 88.86 per cent for the waxed and unwaxed film coated European tablets, respectively. The mean peak plasma concentrations for the U.S. formulations were 176.3 ng ml-1 and 180.1 ng ml-1 compared to 196.3 and 200.1 ng ml-1 for the waxed and unwaxed European formulations, respectively. Mean time to peak plasma concentrations for the two U.S. formulations and the waxed and unwaxed European formulations were 3.22, 3.33, 3.06, and 3.26 h, respectively. In addition, the oral reference solution yielded a mean peak plasma concentration of 222.8 ng ml-1 and a mean time to peak plasma concentration of 2.68 h. Analysis of variance and multiple range comparisons (p less than 0.05) indicated that the tablet formulations were bioequivalent. The results of this study show that the U.S. formulated almitrine bismesylate tablets exceed 85 per cent relative bioavailability with respect to the oral reference solution and are bioequivalent compared to the marketed standard European tablet formulations.

Adult↗
PubMedDate not supplied

One year administration of almitrine bismesylate (Vectarion) to chronic obstructive pulmonary disease patients: pharmacokinetic analysis.

A double blind study utilizing orally administered almitrine bismesylate was conducted involving 36 stable chronic obstructive pulmonary disease (COPD) patients with hypoxia and with and without hypercapnia. The patients received 50 mg tablets twice daily for 360 days. Blood samples were taken both at predose and 3 hours postdose at different periods throughout 1 year dosage regimen and plasma levels were analyzed by a GLC method using a nitrogen-phosphorous detector. Plasma almitrine concentrations indicate large variability at each time sample. Results suggest an increasing trend in the almitrine plasma levels as a function of time. Plasma almitrine levels increased significantly (p less than 0.01) between test day 14 and test day 360 (243 +/- 213 per cent and 199 +/- 170 per cent for predose and 3h postdose samples, respectively) indicating that steady state is not achieved by day 14. Almitrine plasma levels appear to stabilize between test day 90 and test day 180. The effective multiple dose half-life for almitrine bismesylate in plasma is estimated to be 32 days. About half of the patients exhibited steady state peak plasma almitrine levels above 500 ng ml-1. In addition, 19 per cent of the patients achieved maximum apparent steady state almitrine levels greater than 700 ng ml-1. Mean accumulation was estimated to be 4.21 +/- 1.98 at one year.

Almitrine↗
PubMedDate not supplied

Pharmacokinetics of caffeine in breast milk and plasma after single oral administration of caffeine to lactating mothers.

Six healthy lactating women ranging in age from 28 to 35 years were selected to participate in the study. The women had been nursing their infants from 3 1/2 weeks up to 17 weeks. On the morning of the study each participant received 100 mg dose of caffeine. The oral dose of caffeine was taken with a glass of water on an empty stomach. Blood samples were collected from zero time to 24 h after caffeine administration. Each subject aseptically collected breast milk from the right and left breasts by manual expression or using a mechanical breast pump, from zero time to 24 h after caffeine administration. Caffeine in plasma and breast milk was determined by gas liquid chromatography using nitrogen phosphorous detection. Caffeine was rapidly absorbed producing plasma time to peaks ranging from 0.50 to 1.00 h, with values for peak concentrations between 3.60 and 6.15 micrograms ml-1 in plasma. In breast milk, time to peak ranged from 0.75 to 2.00 h and concentration values between 1.98 and 4.30 micrograms ml-1. No significant differences were found between attainment of the time of the peak in plasma and breast milk, p greater than 0.05. In addition, peak concentration for the right and left breast were not statistically different, p greater than 0.05. However, significant differences, p less than 0.05, between plasma and both breasts in regards to the peak concentrations were found. The overall breast milk/plasma ratio obtained from the respective area under the curves were 0.815 +/- 0.0521 and 0.809 +/- 0.202 for the right and left breast, respectively, and no statistical differences were observed between the right and left breasts, p greater than 0.05. In summary, caffeine is rapidly transferred to breast milk. Multiple dose studies are needed to provide more information about caffeine concentration in breast milk of women who receive multiple doses of caffeine or who chronically consume caffeine.

Administration, Oral↗