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

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

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↗

PubMedDate not supplied

The pharmacokinetics of loratadine in normal geriatric volunteers.

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration-time curve, was 146.7 h.ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration-time curve of 394.9 h.ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

Age Factors↗

PubMedDate not supplied

Isolation and identification of the major metabolite of albuterol in human urine.

The major urinary metabolite of albuterol in man was isolated and purified by ion-exchange chromatography and countercurrent distribution. On the basis of proton magnetic resonance, infrared, and mass-spectral analysis, enzymic hydrolysis, and assay of inorganic sulfate after acid hydrolysis, the metabolite has been identified as the 4'-O-sulfate ester of albuterol.

Albuterol↗

PubMedDate not supplied

Absorption, metabolism, and excretion of 14C-tosifen in the dog and rat.

14C-tosifen [N-2-(1-phenylpropyl)-N'-p-tolyl sulfonylurea] was readily absorbed in both rats and dogs. The rates of absorption, metabolism, and urinary excretion were higher in the rat than in the dog. More of the drug was excreted via the feces than in the urine of the rat, whereas in the dog, the drug was primarily excreted into the urine. The parent drug was the major radioactive component in the plasma of both species. In the urine, however, only a negligible amount of tosifen was found. The major urinary metabolite was a hydroxymethyl derivative which accounted for about 60% and 40% of the total radioactivity in the urine of the dog and rat, respectively.

Absorption↗

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↗

PubMedDate not supplied

Placental transfer of quazepam in mice.

The disposition of 14C-quazepam following a single 5-mg/kg po dose was studied at the postembryonic period (day 12 of pregnancy) and near-term (day 18 of pregnancy). In both 12- and 18-day pregnant mice, radioactivity from the quazepam dose was widely distributed in the maternal tissues, with the highest levels in the liver and kidneys. At the time points analyzed (1, 5, and 24 hr post-dose), radioactivity levels in the fetus were consistently 44% of the maternal plasma levels in 12-day pregnant mice. In 18-day pregnant mice, fetal radioactivity levels at these time points were consistently equal to or slightly greater than maternal plasma levels. This indicates that radioactivity was taken up and eliminated from fetal tissues at rates that were reasonably similar to those in corresponding maternal tissues. No accumulation of radioactivity was observed in the fetus or in maternal tissues in either the 12-day or the 18-day pregnant mice. In 18-day pregnant mice, concentrations of quazepam and its metabolites were measured either by gas-liquid chromatography or thin layer radiochromatography. In the maternal plasma, concentrations of quazepam, its first-formed metabolite, 2-oxoquazepam, and 3-hydroxy-2-oxoquazepam were relatively low at all time points; levels of N-desalkyl-2-oxoquazepam and 3-hydroxy-N-desalkyl-2-oxoquazepam (HDOQ) were much higher. Fetal levels of unchanged drug and metabolites were generally less than or equal to maternal plasma levels, except for HDOQ levels, which were higher in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗