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Biomedical subjects

R Gural

Publications and source records attributed to R Gural.

12 recordsLinked to original sources
PubMed1988

Effects of loratadine (SCH 29851) in suppression of histamine-induced skin wheals.

The efficacy and safety of single oral doses (10, 20, 40, and 80 mg) of loratadine (SCH 29851) in suppressing formation of histamine-induced wheals were assessed in a crossover study in 29 healthy male subjects. One hour prior to dosing and 1, 2, 3, 4, 6, 8, 12, 16, 24, 28, 32, 36, 40, and 48 hours after dosing, histamine and saline were injected intradermally into opposite arms. Measurements of resulting wheal areas showed loratadine suppressed wheal formation significantly better than placebo; suppression was dose related. The mean suppression over 48 hours was 16% in placebo-treated subjects and 35%, 45%, 51%, and 67% in the 10, 20, 40, and 80 mg loratadine-treated subjects, respectively. The onset of action occurred within the first hour. Duration of suppression was dose related, ranging from 12 hours with the lowest dose (10 mg) to 48 hours with the higher doses (40 and 80 mg). Incidence of sedation and other side effects were comparable among all doses of loratadine and placebo.

Adolescent↗
PubMed1985

The excretion of rosaramicin in breast milk.

The excretion of rosaramicin, a macrolide antibiotic, was studied in the breast milk of ten lactating women. Breast milk and serum samples were collected for 48 hours after a single 250-mg oral dose of rosaramicin. Mean serum half-life, apparent volume of distribution, and oral clearance were 4.4 hours, 3.41 L/kg, and 6.34 mL/min/kg, respectively. Mean milk/serum ratio was 0.12 and the total amount of drug recovered over the first ten hours was 6.25 micrograms, approximately 0.0025% of the dose. A positive correlation between breast milk volume and breast milk clearance was found, suggesting that the amount of drug received by a nursing infant will depend on the volume of milk produced by the mother. Drug-induced toxicity from the parent drug is unlikely to occur in nursing infants since the amount of rosaramicin that a nursing infant could ingest is small.

Adult↗
PubMed1985

Steady-state bioavailability of dexbrompheniramine and pseudoephedrine from a repeat-action combination tablet.

The steady-state bioavailabilities of dexbrompheniramine and pseudoephedrine were evaluated following multiple-dose administrations of a repeat-action combination tablet containing 6 mg of dexbrompheniramine maleate with 120 mg of pseudoephedrine sulfate every 12 h for 7 d compared with reference standards. The reference standards used in this study were concomitant administration of conventional 2-mg dexbrompheniramine maleate tablets every 4 h and 120-mg pseudoephedrine sulfate repeat-action tablets every 12 h, each for 7 d. Twelve healthy adult male volunteers completed this randomized two-way crossover study. Blood samples for subsequent assay were obtained at frequent time intervals throughout each 7-d dosing phase. Sensitive and specific gas-liquid chromatographic methods were used for the determination of dexbrompheniramine and pseudoephedrine in plasma. Based on the plasma levels, the times to reach steady state were determined. In addition, the major bioavailability parameters (Cmin, Cmax, tmax, and AUC) for days 6 and 7 of dosing were determined and statistically evaluated. The results of this study demonstrate that, at steady state, the repeat-action combination tablet and concomitant administration of the reference standards are bioequivalent.

Biological Availability↗
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↗
PubMed1984

Effect of sleep on quazepam kinetics.

The effect of sleep on quazepam kinetics was studied in 12 normal adult men. In a randomized two-way crossover design, each subject received one 15-mg quazepam tablet either at night just before sleep or in the morning after a night's sleep. Blood samples were drawn before and at specified times (to 120 hr) after dosing. To assure that blood collection did not interfere with sleep, blood was drawn by an indwelling catheter from a large arm vein. Plasma concentrations of quazepam and its two major plasma metabolites (which are also active) 2-oxoquazepam and N-desalkyl-2-oxoquazepam (N-desalkylflurazepam) were determined by specific GLC methods. Kinetic analysis was by a two-compartment open model with first-order absorption/formation kinetics. Quazepam was rapidly absorbed with both administration times; absorption t 1/2 was 0.7 to 0.9 hr. Absorption lag time was slightly longer after the nighttime dose (1.0 and 0.6 hr). Maximum concentration and AUC of quazepam and 2-oxoquazepam and AUC of N-desalkyl-2-oxoquazepam were somewhat higher after nighttime dosing, most likely a result of decreased apparent volume of distribution of the central compartment after the nighttime dose (5.0 l/kg for nighttime dosing and 8.6 l/kg for morning dosing). The elimination t 1/2s of quazepam, 2-oxoquazepam, and N-desalkyl-2-oxoquazepam after the morning dose were 25, 28, and 79 hr, which did not differ from those values after the nighttime dose. In general, time of dosing had no appreciable effect on quazepam kinetics or those of its major active plasma metabolites. The small differences between the two dose times are not expected to have clinical significance.

Absorption↗
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

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 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↗
PubMedDate not supplied

Comparative steady state bioavailability of conventional and controlled-release formulations of albuterol.

A new controlled-release (CR) dosage formulation of albuterol has been developed which is suitable for twice-a-day dosing. The present study was conducted in twelve healthy adult male volunteers to compare the steady state plasma levels obtained following repeated administration of a 4 mg CR tablet (q12h) compared to a 2 mg conventional table (q6h) for 5 consecutive days. The mean steady state plasma level-time curves for both the CR and conventional tablet treatments were comparable over time and reproducible. There were no significant differences in the AUC or Cmax values between the two treatments. The mean 48-h AUC values were 240.7 and 231.3 h X ng ml-1 for the conventional and CR tablets, respectively, while the corresponding Cmax values ranged from 5.3 to 6.8 ng ml-1 and 5.4 to 6.5 ng ml-1. There were no significant differences in Cmin values except for one 12-h (day 4) value. Cmin values ranged from 3.8 to 4.3 ng ml-1 and 3.0 to 4.8 ng ml-1 for the conventional and CR tablets, respectively. The data show that the 4 mg albuterol CR tablet (q12h) is bioequivalent to a 2 mg conventional albuterol tablet (q6h). The CR tablet formulation will offer the advantage of increased patient compliance; additionally, the CR formulation may prove to be especially beneficial in the treatment of nocturnal asthma.

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

Disposition and metabolic fate of 14C-quazepam in man.

The absorption, metabolism, and excretion of quazepam, a new benzodiazepine hypnotic, was investigated in six normal male volunteers after oral administration of 25 mg 14C-quazepam in solution. Quazepam was well absorbed. Plasma radioactivity peaked (324.6 ng quazepam eq/ml) 1.75 hr postdose. Unchanged quazepam reached its maximum plasma level (148 ng/ml) at 1.5 hr with an apparent absorption half-life of 0.4 hr. Major plasma metabolites of quazepam were 2-oxoquazepam (OQ), obtained by replacement of S by O,N-desalkyl-2-oxoquazepam (DOQ), and 3-hydroxy-2-oxoquazepam (HOQ) glucuronide. Both OQ and DOQ are pharmacologically active. Plasma elimination half-lives for quazepam, OQ, DOQ, and radioactivity were 39, 40, 69, and 76 hr, respectively. The respective AUC (120 hr) values were 715, 438, 3323, and 11402 hr X ng/ml. Approximately 54% of the radioactive dose was excreted in the urine (31.3%) and feces (22.7%) over a 5-day period. HOQ glucuronide was the major urinary metabolite of quazepam. Other metabolites present in the urine in relatively large amounts were glucuronides of DOQ and HDOQ.

Adult↗