Biomedical subjects

E Radwanski

Publications and source records attributed to E Radwanski.

At least 55 records · Page 3Linked to original sources

PubMed1988

Secretion of dilevalol in breast milk.

The pharmacokinetics of unchanged and total (unchanged plus Glusulase [Biotechnology Systems, Boston, MA]) released dilevalol and secretion into human breast milk was studied in six healthy breast-feeding female volunteers administered a single 400-mg dilevalol hydrochloride capsule. In plasma, the mean Cmax for unchanged dilevalol, 485 ng/mL was reached at 0.8 hour (tmax) and the AUC(48 hours) was 1435 hr X ng/mL. Pharmacokinetic analysis of unchanged dilevalol in plasma showed that dilevalol was distributed and eliminated with half-lives of 0.9 and 8.2 hours, respectively. Breast milk concentrations of unchanged dilevalol as a function of time, paralleled those of plasma but were consistently lower. The milk Cmax, 149 ng/mL, occurred during the 0 to 2 hour collection interval; the AUC(42 hours) for unchanged dilevalol in milk was 663 hr X ng/mL. The mean milk to plasma concentration ratio was 0.46. The unchanged dilevalol plasma concentrations were 12 to 18% those of total drug suggesting that the drug is extensively conjugated. By contrast, the concentrations of unchanged dilevalol in breast milk, based on Cmax and AUC data were 63 to 94% those of total drug, indicating that very little conjugated drug is secreted into breast milk. Through 48 hours, a mean of only 27 micrograms dilevalol or 0.007% of the administered dose was secreted into breast milk, which is much less than that reported for other beta blockers.

Administration, Oral↗

PubMed1987

Loratadine: multiple-dose pharmacokinetics.

The steady-state pharmacokinetics of loratadine (L), a new long-acting antihistamine devoid of CNS activity, was investigated in 12 healthy male volunteers. Each volunteer received 40-mg L capsules q24h for ten days. Blood samples were collected at various times on day 1, 5, 7, and 10 and assayed for L by radioimmunoassay (RIA) and for descarboethoxyloratadine (DCL), a known active metabolite, by high-performance liquid chromatography (HPLC). The plasma L and DCL concentration-time data in the disposition phases were fitted to a biexponential equation for pharmacokinetic analysis. Steady-state plasma L Cmax concentrations were reached at 1.5 hour (Tmax) after each dose. DCL steady-state Cmax values ranged 26 to 29 ng/mL at a Tmax ranging from 1.8 to 3 hours. The AUC at steady state, AUC tau, was 80 to 96 and 349 to 421 h X ng/mL for L and DCL, respectively. The accumulation indexes (Ra) based on AUC tau ratios, did not change for either compound after day 5. Ra values for L and DCL after the fifth dose were 1.4 and 1.9, respectively, indicating that there is little accumulation of either L or DCL after a multiple (once-a-day) dosage regimen. The t1/2 beta at steady state were 14.4 and 18.7 hours for L and DCL, respectively, which were similar to those reported following a single-dose L administration. Observed plasma drug concentrations were in good agreement with predicted values derived for pharmacokinetic parameters.

Adult↗

PubMed1987

Pharmacokinetics and dose proportionality of loratadine.

The dose proportionality and pharmacokinetics of loratadine, a new nonsedating antihistamine, were studied in 12 normal volunteers. In a three-way cross-over, each volunteer received a single 10-, 20-, or 40-mg loratadine capsule. Blood was collected up to 96 hours after dosing. Plasma loratadine concentrations were determined by radioimmunoassay (RIA), and those of a minor, but active metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Concentrations in the disposition phase were fitted to a biexponential equation for pharmacokinetic analysis. For dose proportionality, AUC- and Cmax-dose relationships were evaluated by linear regression. Also, pharmacokinetic parameters and dose-adjusted AUCs were compared by analysis of variance. Loratadine was rapidly absorbed, reaching Cmax values (4.7, 10.8, and 26.1 ng/mL) at 1.5, 1.0 and 1.2 hours for the 10-, 20-, and 40-mg doses, respectively. The loratadine t1/2 beta ranged from 7.8 to 11.0 hours. Descarboethoxyloratadine reached Cmax values (4.0, 9.9, and 16.0 ng/mL) at 3.7, 1.5, and 2.0 hours for the 10-, 20-, and 40-mg doses, respectively. Its t1/2 beta ranged from 17 to 24 hours. For both compounds, AUC- and Cmax-dose relationships were linear and there were no differences in the t1/2 beta, CL/F, or dose-adjusted AUC values among the treatments. Loratadine and descarboethoxyloratadine plasma concentrations and pharmacokinetics were not dose dependent.

Administration, Oral↗

PubMed1987

Pharmacokinetics and metabolism of an intravenously administered penem (Sch 34343) in humans.

The pharmacokinetics of Sch 34343, a new broad-spectrum penem antibiotic, was studied in subjects receiving 1 g of 14C-labeled drug by intravenous administration. At the end of a 30-min intravenous infusion, the mean maximum concentration of drug in serum was 39 micrograms/ml for unchanged Sch 34343 and 49 mu eq/ml for total radioactivity. The mean serum half-lives of Sch 34343 were 0.16 h for the distribution phase and 0.80 h for the elimination phase. The total body clearance of Sch 34343 was 7.52 ml/min per kg, and the mean apparent volume of distribution was 525 ml/kg. Over a 4-day period, mean urinary excretion of radioactivity accounted for 87.9% of the dose, and mean urinary excretion of unchanged Sch 34343 accounted for 23.6% of the dose. The total radioactivity in feces on days 0 to 6 accounted for only 0.8% of the dose. In serum from 0.5 and 1 h, unchanged Sch 34343 represented the major radioactive peak, with negligible amounts of several metabolites. In urine, there were at least six metabolites in addition to Sch 34343. The amount of unchanged Sch 34343 accounted for 33% of radioactivity in samples of urine from 0 to 2 h, 22% in urine from 2 to 4 h, 15% in urine from 4 to 8 h, and 0% in urine from 8 to 12 h.

Adult↗

PubMed1986

Pharmacokinetics and metabolism of [14C]rosaramicin in dogs.

The pharmacokinetics and metabolism of [14C]rosaramicin were studied in dogs after intravenous (i.v.; 10 mg/kg [bodyweight]) and oral (25 mg/kg) administration. After i.v. administration, rosaramicin levels in plasma declined rapidly, with half-lives of 0.22 h for the distribution phase and 0.97 h for the elimination phase. The apparent volume of distribution was 3.43 liters/kg, and the total body clearance was 106 mg/min . kg, indicating extensive distribution in tissue or metabolism or both. The absorption of oral solution was 58%, and the absolute bioavailability of rosaramicin was 35%. The plasma area under the curve of unchanged rosaramicin was only 5% that of total radioactivity after oral administration and 8% after i.v. administration, indicating extensive metabolism of the drug. The total radioactivity excreted in urine accounted for only 24% of the i.v. dose and 17% of the oral dose. Fecal radioactivity accounted for 71% of the i.v. dose and 68% of the oral dose. Several metabolites were observed in the plasma and urine. The amount of unchanged rosaramicin in urine (1 to 2% of the dose) was quite small after drug administration by either route.

Administration, Oral↗

PubMed1985

Comparative bioavailability and pharmacokinetics of three formulations of albuterol.

Albuterol sulfate, alpha'[[1,1-dimethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol sulfate, is a relatively selective beta-2-adrenergic bronchodilator used for the relief of bronchospasm. The bioavailability of two 4-mg tablet formulations, differing in their inactive excipients, and a syrup formulation, was evaluated. The three dosage forms were orally administered to 12 normal male volunteers in a randomized three-way crossover study. Plasma samples were collected at frequent time points through 12 h and analyzed for albuterol content by a specific GC-MS method. The drug was rapidly absorbed from all three formulations. Maximum drug concentrations were comparable for the three formulations and were obtained between 1.8-2.0 h. The areas under the plasma concentration-time curves were 68-78 h X ng/mL. The drug elimination phase half-live (t1/2 beta) ranged from 4.8 to 5.5 h. Analysis of the data showed that the bioavailability of albuterol from a tablet formulation is equivalent to that from a solution.

Administration, Oral↗

PubMed1985

Clinical pharmacology of netilmicin in preterm and term newborn infants.

Sixty-four neonates, with gestational age ranging from 27 1/2 to 40 weeks, postnatal age from 1 to 15 days, and birth weight from 800 to 3400 gm, were given netilmicin 2.5 mg/kg intramuscularly two or three times per day according to postnatal age, for 5 to 14 days. Serum concentrations were measured before and 1 hour after a dose at least twice during treatment. The serum washout profile of the drug was observed in 22 neonates after discontinuation of therapy. Renal function was studied in 37 infants by measuring serum creatinine concentrations and in 27 by urinary excretion of N-acetyl-glucosaminidase during and up to 15 days after therapy. Behavioral and impedance audiometry, and in infants failing those, auditory brainstem evoked response tests, were performed between 6 and 12 months of age. In 23.5% of the neonates, trough serum levels were greater than 3 micrograms/ml. The serum washout followed a multiexponential decay, accounting for distributional, rapid (initial), and slow (tissue) elimination phases. Linear regression analysis performed between each kinetic parameter and gestational age or birth weight showed that initial elimination half-life, steady-state volume of distribution, and total body clearance were significantly correlated with both variables. Netilmicin did not cause detectable renal or auditory damage.

Acetylglucosaminidase↗

PubMed1985

Interspecies pharmacokinetic scaling of Sch 34343.

Pharmacokinetic parameters of Sch 34343 have been determined for mice, rats, rabbits, monkeys, dogs and humans and correlated among species as an exponential function of body weight. The pertinent pharmacokinetic parameters tested are apparent and steady-state volumes of distribution, total body clearance, elimination phase half-life, and mean residence time. This study showed that the extrapolation of animal data to humans on a new investigational drug, Sch 34343, can be potentially useful.

Animals↗

PubMed1984

Multiple-dose halazepam kinetics.

Halazepam is a benzodiazepine used in the management of anxiety disorders or short-term relief of anxiety. Our study was undertaken to evaluate its steady-state kinetics and those of its major active plasma metabolite N- desalkylhalazepam . Eleven healthy men aged 19 to 35 yr were given oral, 40-mg halazepam tablets every 8 hr for 14 days. Plasma samples were analyzed by gas chromatography to determine levels of halazepam and N- desalkylhalazepam . Halazepam kinetics can best be described by a two-compartment open model with first-order absorption kinetics. The elimination phase t1/2s of halazepam and N- desalkylhalazepam were 34.7 and 57.9 hr. Steady-state levels were predictable from kinetic data and were reached by the third day for halazepam and by the eleventh day for N- desalkylhalazepam .

Adult↗

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

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↗

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↗

PubMedDate not supplied

Multiple-dose albuterol kinetics.

Albuterol, a beta-adrenergic agonist bronchodilator, was studied in 12 healthy male volunteers to evaluate the steady-state pharmacokinetics following oral administration of 4-mg tablets, given every six hours for five days. The kinetics of albuterol were best described by a two-compartment open model with first-order absorption kinetics. Steady-state plasma levels were predictable from the kinetic data and were reached by the third day of dosing (ninth and tenth dose). Small accumulation ratios of approximately two were seen based on area under the plasma concentration-time curve and maximal and minimal concentration data. The elimination phase half-life was determined to be 6.5 hours, which is similar to the values reported following single-dose administration.

Adolescent↗

PubMedDate not supplied

Pharmacokinetics of interferon alpha-2b in healthy volunteers.

In a three-way crossover design, 12 healthy male volunteers received 5 X 10(6) IU/m2 body surface area interferon alpha-2b(IFN alpha-2b) by intravenous (IV) infusion over 30 minutes, intramuscular (IM) injections, and subcutaneous (SC) injections. Blood and urine samples were collected at specified times, and analysis of IFN alpha-2b concentrations was performed by immunoradiometric assay. "Flulike" symptoms were the most frequently reported adverse experiences and were independent of the route of administration. After a 30-minute IV infusion, IFN alpha-2b disappeared rapidly from serum, with distribution and elimination phase half-lives of 0.1 hour and 1.7 hours, respectively. Interferon alpha-2b was absorbed slowly after IM and SC administration, with similar absorption half-lives of 5.8 and 5.5 hours, respectively. The observed maximal concentrations after IM and SC administration were 42.1 IU/mL at six hours and 45.8 IU/mL at eight hours, respectively. Interferon alpha-2b was eliminated with half-lives of 2.2 hours after IM administration and 2.9 hours after SC administration. The areas under the serum concentration-time curves for the SC and IM doses were higher than those obtained for the IV infusion. Measurable amounts of IFN alpha-2b were not found in urine regardless of the route of administration.

Adult↗

PubMedDate not supplied

Pharmacokinetics of isosorbide-5-mononitrate after oral administration of an extended-release mononitrate formulation versus a standard dinitrate formulation.

The steady-state pharmacokinetic profile of isosorbide-5-mononitrate (5-ISMN) after oral administration of an extended-release tablet formulation of 5-ISMN 60 mg or 120 mg once a day was compared with that after administration of isosorbide dinitrate (ISDN) 40 mg every 6 hours, in a randomized, open-label, three-way crossover trial in 24 healthy men. After oral administration of extended-release 5-ISMN 60 mg or 120 mg once daily, 5-ISMN was slowly absorbed, reaching mean peak plasma concentrations of 557 and 1151 ng/mL, respectively, in approximately 3 hours. Plasma concentrations of 5-ISMN were dose proportional between 60 mg and 120 mg. After oral administration of ISDN 40 mg every 6 hours, a mean peak plasma 5-ISMN concentration of 806 ng/mL was achieved in less than 2 hours (mean time to reach the maximum plasma concentration was 1.5 hours). The mean plasma apparent elimination half-life of 5-ISMN was 6.2 hours after extended-release 5-ISMN administration and 7.1 hours after ISDN. Although the maximum plasma concentration was higher and the minimum plasma concentration was lower after administration of extended-release 5-ISMN 120 mg once daily compared with ISDN 40 mg every 6 hours, there was no significant difference (P > 0.05) in the "bioavailability" of 5-ISMN between these two treatments. The most commonly reported adverse events in these "nitrate-naive" subjects were headache, dizziness, nausea, and vomiting; these were dose related and their incidence decreased with repeated exposure.

Administration, Oral↗

PubMedDate not supplied

The pharmacokinetics of ceftibuten in humans.

The pharmacokinetics of ceftibuten, a new oral cephalosporin, has been studied in humans. Ceftibuten is very well absorbed in young and old patients. Absorption may be slightly decreased by food or relatively high doses (800 mg). The pharmacokinetics have been well characterized in rising single-dose and multiple-dose studies. The half-life is relatively long for this class of drugs, being approximately 2-3 hr. Apparent plasma clearance (CL/F), is approximately 40-75 ml/min, and the renal clearance is approximately 30-50 ml/min, corresponding to the fraction excreted unchanged in the urine of approximately 60%-70% of the dose. The apparent volume of distribution after oral dosing (Vd/F) was approximately 0.2 L/kg. The half-life, plasma clearance, renal clearance, and fraction excreted in urine are not affected by increasing dose and are constant during multiple dosing. There is little drug accumulation during multiple dosing. Drug elimination is decreased in patients with renal insufficiency and dosing in these patients should be adjusted relative to creatinine clearance values. The drug penetrates very well to experimentally induced inflammatory fluid but produces negligible levels in breast milk. The drug has no effect on the pharmacokinetics of theophylline. The drug is well tolerated and has pharmacokinetic properties that are clinically advantageous.

Absorption↗