Biomedical subjects

K S Albert

Publications and source records attributed to K S Albert.

At least 19 recordsLinked to original sources

PubMed1989

Pharmacokinetics of flurbiprofen in man. II. Plasma protein binding.

The plasma protein binding of flurbiprofen was studied using equilibrium dialysis. Dialysis was carried out using plasma samples obtained from five of 15 subjects participating in a crossover bioavailability study. During the course of this study subjects received doses of 100, 200, and 300 mg of flurbiprofen as tablets, and 100 mg as an aqueous solution. Seven samples from each of the four treatments (28 samples/subject) were utilized. An additional 14 samples (seven concentrations prepared in duplicate were prepared using blank plasma obtained from each subject. Concentrations of bound (Cbd) and free (Cfd) flurbiprofen were determined at dialysis equilibrium using a radiotracer technique. Binding curves were constructed for each subject using data obtained from these 42 (28 ex vivo and 14 in vitro) samples. The data was well fitted to a modified Scatchard equation with the addition of a linear term. Although the plasma protein binding of flurbiprofen was nonlinear, within the range of concentrations encountered in the clinical setting, it is minimally so. The Cb/Cf ratio averaged 1524, indicating that in plasma, flurbiprofen is greater than 99.9% bound. The results support the observation that for doses of flurbiprofen usually encountered clinically, the drug obeys linear kinetics.

Adult↗

PubMed1986

Ibuprofen kinetics in plasma and synovial fluid of arthritic patients.

After administration of a single dose and at steady state, ibuprofen concentrations were measured simultaneously in plasma and synovial fluid obtained from eight patients with rheumatoid arthritis. By seven hours after a dose at steady state, the mean synovial fluid: plasma ibuprofen concentration ratios were constant, and the synovial fluid levels were, on average, greater than those in plasma. The extent to which ibuprofen was bound to protein was somewhat greater in plasma than in synovial fluid. As a result, the mean synovial fluid:plasma free concentration ratio for seven-hour and later specimens was greater than that based on total concentrations. The degree of accumulation of ibuprofen in each fluid was minimal, consistent with its short half-life.

Adult↗

PubMed1986

The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites.

The pharmacokinetics of ibuprofen and its two major metabolites, the hydroxy and carboxy derivatives, were studied in seven functionally anephric subjects undergoing hemodialysis therapy. Subjects received ibuprofen 800 mg tid for 14 days. Hemodialysis was performed three times weekly during this period. Arterial and venous blood samples were collected before dialysis and along with dialysate, and during the final dosing interval and dialysis session. No accumulation of ibuprofen plasma concentrations and an absence of intact ibuprofen in dialysate indicated clearance through metabolic pathways. The metabolites did accumulate significantly (mean plasma levels, carboxy 249 micrograms/mL and hydroxy 57 mu/mL); however, both were detected in dialysate. Mean extraction efficiencies were 0.16 (hydroxy) and 0.15 (carboxy). Dialysis clearance calculated by arterial-venous difference was found to agree with actual recovery in dialysate for both metabolites. Side effects were not observed in any subject.

Adult↗

PubMed1986

Pharmacokinetic disposition of 14C-glyburide in patients with varying renal function.

The pharmacokinetics of 14C-labeled glyburide were studied in 13 men with varying degrees of renal impairment. Patients received a single, 5 mg oral dose of glyburide as a solution (10 microCi/ml/mg) after a high-carbohydrate breakfast. Serial plasma and breath samples were collected for 48 hours and urine and feces were collected for 5 to 7 days. Patients with normal to moderately impaired renal function (creatinine clearance [CLCR] of 29 to 131 ml/min/1.7 m2) had glyburide plasma t1/2 values of 2.0 to 5.0 hours, with no relationship between CLCR and glyburide clearance. One subject with severe renal impairment (CLCR = 5 ml/min/1.7 m2) had decreased glyburide clearance that resulted in a t1/2 of 11 hours. The elimination of metabolites was more dependent on renal status but was only significantly affected in the patient with severe renal impairment.

Absorption↗

PubMed1985

Liquid chromatographic assay for fluoxymesterone in human serum with application to a preliminary bioavailability study.

Fluoxymesterone was extracted from serum with a liquid-liquid extraction procedure. Serum containing both drug and internal standard, 6 alpha-methylprednisolone, was extracted with methylene chloride. The extract was washed with 0.1 M NaOH and water, evaporated, and reconstituted with mobile phase. Chromatography was performed on a Zorbax Sil column, preceded by a guard column, with a mobile phase composed of 50% water-saturated butyl chloride:tetrahydrofuran:methanol:phosphoric acid (880:100:15:0.5). Fluoxymesterone and methylprednisolone were detected by UV absorption at 236 nm. Overall recovery was 80%. Calibration curves were linear for fluoxymesterone concentrations from 5 to 100 ng/mL. The assay is accurate and precise (RSD values less than or equal to 7%); endogenous steroids did not interfere with the assay. Assay suitability was assessed in a bioavailability study in which six subjects each received two treatments of 10-mg fluoxymesterone tablets in a Latin-square crossover study. The two treatments were a tablet administered either buccally or orally. Cmax values ranged from 40 to 150 ng/mL with tmax values of 1-2 h. The harmonic mean half-life of fluoxymesterone was 2.0 h. Less than 8% of the AUC was extrapolated. Mean Cmax and AUC values from the oral treatment were 80 and 76%, respectively, of the mean values from the buccal treatment.

Adult↗

PubMed1985

Effect of food and tablet age on relative bioavailability and pharmacodynamics of two tolbutamide products.

Relative bioavailability and pharmacodynamics of tolbutamide from two different commercially available tablet products have been evaluated in healthy subjects in a single-dose crossover study. "Fresh" tablets and tablets aged by exposure to 98% relative humidity for 3 d at ambient temperature were studied. Aging was found to differentially affect both the rate and extent of absorption for the two products. Differences were reflected by log AUC (generic product AUC 10% lower than the product of the innovator, p = 0.047), peak concentration (generic product 27% lower than the product of the innovator, p = 0.0001), mean absorption time (generic product 119% longer than the product of the innovator, p = 0.0008), and mean residence time (generic product 17% longer than the product of the innovator, p = 0.011). Aged product from the innovator produced statistically significantly higher serum tolbutamide concentrations for the first 8 h postdose and a greater glucose depression than aged generic product. Administration of unaged tablets with food produced differences in the rate of absorption, manifested in time-to-peak (generic product 69% later than the product of the innovator, p = 0.006), peak concentration (generic product 18% lower than the product of the innovator, p = 0.001), and mean absorption time (generic product 104% greater than the product of the innovator, p = 0.007), which resulted in statistically significantly higher tolbutamide concentrations for the product of the innovator than for the generic product for the first 3 h postdose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Pharmacokinetics of ibuprofen.

The pharmacokinetics of ibuprofen (Motrin) are best described by a two-compartment open model. Ibuprofen pharmacokinetics are only minimally influenced by advanced age, the presence of alcoholic liver disease, or rheumatoid arthritis. Levels of ibuprofen in breast milk are negligible. In addition, ibuprofen can be combined with acetaminophen without altering the pharmacokinetic profile. However, although not yet clinically proved, the concomitant use of ibuprofen and aspirin appears to reduce ibuprofen plasma levels to less than half those observed with ibuprofen alone.

Acetaminophen↗

PubMed1984

Effects of age on the clinical pharmacokinetics of ibuprofen.

The pharmacokinetics of ibuprofen (Motrin) were studied in 17 normal elderly men and women aged 65 to 78 years. Total and free unbound plasma concentrations of ibuprofen were determined 12 hours after single oral doses of 400, 800, and 1,200 mg. These results were then compared with those of a similar study involving 15 normal young men 22 to 35 years old. The two age groups showed no statistically significant differences in any pharmacokinetic parameter studied. Therefore, according to this study, advanced age has only minimal influence on the pharmacokinetics of ibuprofen, and dosage apparently does not need to be adjusted for age.

Adult↗

PubMed1984

Excretion of ibuprofen into breast milk.

Concentrations of ibuprofen in breast milk and serum were compared in 12 patients who had ingested one 400 mg tablet of ibuprofen every 6 hours over a 24-hour period for relief of post-cesarean section pain. Samples of breast milk and blood were obtained simultaneously over a 34-hour period beginning just prior to the first dose of ibuprofen. Gas-liquid chromatography assay methodology capable of detecting 1 microgram/ml was used to determine concentrations of ibuprofen in serum and breast milk. Ibuprofen was present in the serum with a half-life of approximately 1.5 hours. No measurable amounts of ibuprofen were found in the samples of breast milk. The conclusion drawn is that, in lactating women who take up to 400 mg of ibuprofen every 6 hours, less than 1 mg of ibuprofen per day is excreted in breast milk.

Adult↗

PubMed1984

Determination of ibuprofen in capillary and venous plasma by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic (HPLC) method is described which determines ibuprofen in human capillary or venous plasma. Ibuprofen plus the internal standard, flurbiprofen, were extracted from acidified plasma with pentane-ether, back-extracted into base, and then extracted into the pentane-ether solution after acidification of the aqueous phase. A reverse-phase octadecylsilane column with acetonitrile-water-phosphoric acid as mobile phase and UV detection provided a quantifiable peak for 1 microgram/mL of ibuprofen in 0.1 mL of plasma. Capillary and venous plasma level curves were virtually superimposable after administration of 400 mg of ibuprofen to four normal volunteers. No ibuprofen was detected in the saliva of the subjects.

Capillaries↗

PubMed1984

Determination of flurbiprofen in human serum by reverse-phase high-performance liquid chromatography with fluorescence detection.

A reverse-phase high-performance liquid chromatographic method is described for the determination of flurbiprofen in human serum. Flurbiprofen is extracted from hydrochloric acid-acidified serum with pentane-ether (80:20). An octadecylsilane column was used with a mobile phase of acetonitrile-water-phosphoric acid (650:350:0.5, v/v/v). A fluorescence detector with excitation at 250 nm and emission at 315 nm provided a quantifiable peak for 0.1 microgram/mL of flurbiprofen in 0.5 mL of plasma. A comparison between UV and fluorescence detection systems is presented. The method is applicable to human bioavailability and pharmacokinetic studies with flurbiprofen.

Chromatography, High Pressure Liquid↗

PubMed1984

Pharmacokinetics of ibuprofen in man IV: absorption and disposition.

Fifteen normal male volunteers received 400, 800, and 1200 mg doses of ibuprofen as 1, 2, or 3 tablets, respectively, in crossover fashion, then 420 mg in solution form during the fourth week. Plasma concentration of ibuprofen was measured by an HPLC method. Individual subject concentration-time (C,t) data following the solution were analyzed by two different methods, and results unequivocally indicated the open two compartment model with first order absorption. However, the computer fitting of both arithmetic and geometric mean concentrations led to a different model. A method was developed to obtain absorption data (fraction of drug absorbed, Fa, versus time) for a multicompartmental system from oral data alone, without intravenous data. The method assumes that Vp is constant intrasubject and that absorption is complete following administration of both the solution and tablets. The method was successfully applied to the ibuprofen tablet data. It was shown also that such a method is necessary to obtain ibuprofen absorption data since intrasubject variation of the microscopic rate constants k12, k21, and kel (as reflected by the intrasubject variation of the hybrid rate parameters lambda 1 and lambda 2 or beta and alpha) is of the same order of magnitude as intersubject variation. Absorption of ibuprofen from tablets was shown not to be simple first order as for the solution. The absorption profiles following one tablet were S-shaped, while those following 2 or 3 tablets had partial linear segments indicating zero order absorption.

Absorption↗

PubMed1983

Influence of route of administration on the pharmacokinetics of methylprednisolone.

This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus; (b) as a 1 ml i.m. injection; (c) administered as an oral solution; and (d) as 5 X 8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.

Absorption↗

PubMed1983

Pharmacokinetics of ibuprofen in man--III: Plasma protein binding.

Plasma protein binding of ibuprofen was measured by equilibrium dialysis on 406 plasma samples collected from 15 normal volunteers following doses of 400, 800, and 1200 mg of ibuprofen as tablets (N = 102, 100, 104, respectively) and 420 mg as an aqueous solution (N = 100). Individual subject bound concentration at dialysis equilibrium (Cbd) vs. free concentration at dialysis equilibrium (Cfd) were well fitted via computer to the Scatchard equation with one class of binding sites. The binding capacity averaged 1231 microM (range 848-1658 microM), and the association constant averaged 1.76 X 10(5) M-1 (range 1.15 X 10(5) to 2.73 X 10(5) M-1). Distributional analysis was performed on the free fraction (fd) and bound/free ratios (Cbd/Cfd = 1/fd-1) at dialysis equilibrium for each treatment. Using pooled data of all four treatments, distributional analysis was also performed on the free fractions (f) and bound/free ratios (Cb/Cf = 1/f-1) corresponding to the plasma drug concentrations in blood as it was withdrawn from the subjects. The bound/free ratios were normally distributed, whereas the distributions of the free fractions were skewed towards higher values.

Adult↗

PubMed1983

Pharmacokinetics of ibuprofen in man. I. Free and total area/dose relationships.

Ibuprofen kinetics were studied in 15 subjects after four oral doses. Plasma levels of both total and free ibuprofen were measured for 12 hr, and urine was collected for 48 hr after the doses. All subjects showed a nonlinear relationship between dose and total ibuprofen plasma AUC. Free ibuprofen plasma AUC, however, was linearly related to the dose, suggesting that oral clearance based on free drug was dose independent. Urinary recovery data indicated that efficiency of absorption was dose independent.

Administration, Oral↗

PubMed1983

Ibuprofen and sulindac kinetics in alcoholic liver disease.

Ibuprofen and sulindac kinetics after oral doses were compared in 15 patients with alcoholic liver disease and 29 normal subjects. The patients with alcoholic liver disease were divided into a group with fair hepatic function (FHF) and a group with poor hepatic function (PHF) based on elimination rates of indocyanine green. The effects of alcoholic liver disease on the ibuprofen kinetics were minimal. The absorption of the drug appeared to be delayed in some of the PHF patients, and slight differences were noted in the serum AUC and the elimination rate constant for ibuprofen. The absorption of sulindac was delayed in both PHF and FHF groups of patients, as was the appearance of the active metabolite, sulindac sulfide, and the inactive metabolite, sulindac sulfone. The plasma AUC for sulindac sulfide in patients with poor hepatic function was four times that in normal subjects. The kinetics of sulindac, a pro-drug that relies on the liver for conversion to an active metabolite, were markedly affected by alcoholic liver disease.

Administration, Oral↗

PubMed1983

Ibuprofen and acetaminophen kinetics when taken concurrently.

We evaluated kinetics of ibuprofen and acetaminophen taken concurrently by 20 healthy adults in a randomized crossover design. Steady-state blood levels of ibuprofen and acetaminophen were measured by gas-liquid chromatography and HPLC. There were no significant differences in any of the ibuprofen serum concentrations, but there were differences in acetaminophen serum concentrations in 5 of 19 sampling times. When bioavailability and kinetic parameters for both drugs were compared, there were no significant differences. Our data demonstrate that steady-state kinetics of ibuprofen and acetaminophen are not changed when taken concurrently.

Absorption↗

PubMed1983

The bioavailability of an orally administered medroxyprogesterone acetate suspension.

The relative bioavailability of an orally administered aqueous suspension of medroxyprogesterone acetate (MPA) intended for intramuscular injection (Depo-Provera) was determined in relation to orally administered tablets. Serum levels of MPA were determined by radioimmunoassay following the administration of 400-mg doses to 19 adult male volunteers in a crossover design after an overnight fast. The two treatments were judged bioequivalent based upon a comparison of the resultant MPA serum levels and the derived bioavailability parameters. Hence, the intramuscular suspension administered orally offers an alternative means of achieving optimal serum levels of MPA in patients requiring high dose therapy.

Administration, Oral↗