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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↗
PubMed1979

Rectal and oral absorption of methylprednisolone acetate.

Rectal absorption of methylprednisolone acetate and oral absorption of methylprednisolone and methylprednisolone acetate were investigated in a single-dose 3-way crossover study of 12 normal male volunteers. The median value of bioavailability (relative to oral dose) of methylprednisolone acetate based on unchanged methylprednisolone plasma levels was 14.2% after rectal administration, suggesting that the drug exerts its therapeutic effect topically rather than systemically. In contrast, the median of total radioactivity in urine (as a percentage of rectal dose) was 34.3% (range, 4.52% to 58.8%), suggesting partial bacterial metabolism in the rectum prior to absorption. Mean bioavailability (relative to oral administration of methylprednisolone acetate) of methylprednisolone after oral administration was 89.9%, indicating somewhat better systemic availability of the ester than the alcohol. The average apparent elimination rate constant for methylprednisolone after oral administration of both ester and alcohol was 0.290 hr-1, corresponding to a half-life of 2.39 hr.

Absorption↗
PubMed1979

Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidiarrheal mixture.

Oral coadministration of a single 250-mg tetracycline capsule and 60 ml of a bismuth subsalicylate antidiarrheal mixture reduced tetracycline absorption by 34% without appearing to perturb its absorption or disposition rate. A pronounced increase in intersubject tetracycline absorption variability also was noted. Apparently, the reduction in tetracycline bioavailability previously reported with a kaolin-pectin suspension is not peculiar to kaolin-pectin but can be expected with almost any antidiarrheal whose mechanism of action is adsorptive in nature.

Adult↗
PubMed1979

Double Latin square study to determine variability and relative bioavailability of methylprednisolone.

The variability and relative bioavailability of methylprednisolone tablets were evaluated utilizing a double Latin square crossover design in which each of 20 subjects was given four of five treatments. Three different lots of methylprednisolone tablets exhibited virtually identical absorption, with similar ranges and coefficients of variation of some selected bioavailability parameters indicative of lot-to-lot uniformity in bioavailability. Within-lot and between-lot uniformities in bioavailability also were similar, suggesting that the observed variability in serum methylprednisolone levels was not due to manufacturing process variables. With respect to intra-versus intersubject variability, no differences were found for the absorption rate or terminal half-life. In contrast, between-subject variability associated with extent of absorption was greater than that within subjects. Relative to an aqueous suspension, methylprednisolone tablets were fully bioavailable.

Adult↗
PubMed1978

Pharmacokinetic evaluation of a drug interaction between kaolin--pectin and clindamycin.

The effect of a kaolin--pectin antidiarrheal suspension on the bioavailability of orally administered clindamycin was evaluated by model-dependent pharmacokinetic techniques. Each subject's serum clindamycin concentration--time data in the absence of the kaolin--pectin suspension were fitted to a one-compartment open model with first-order absorption and lag time. The resulting disposition parameters were used to construct individual Wagner-Nelson absorption profiles, expressed as the cumulative relative fraction of clindamycin absorbed versus time following combined antidiarrheal--antibiotic therapy. For each subject, absorption persisted to varying degrees through 14 hr. On the average, the half-time for absorption was prolonged 20-fold (from about 16 min to more than 300 min). In contrast, extrapolation of the individual time courses of relative absorption to infinity revealed that the antidiarrheal had no effect on the extent of clindamycin absorption.

Adult↗
PubMed1978

Influence of kaolin--pectin suspension on digoxin bioavailability.

The effect of a kaolin--pectin suspension on the bioavailability of orally administered digoxin was evaluated when both drugs were given concomitantly and when their time of administration was separated by 2 hr. Coadministration of the antidiarrheal with the cardiac glycoside delayed absorption of the latter and, at the same time, decreased by 62% the amount of drug absorbed. Intersubject variation in digoxin bioavailability also was increased more than twofold. When the kaolin--pectin suspension was given 2 hr before the cardiac glycoside, the digoxin absorption rate was not affected, although its relative extent of absorption was reduced by about 20%. In contrast, when the antidiarrheal was given 2 hr after digoxin, neither the rate nor the extent of absorption of the cardiac glycoside was perturbed. No change in the intersubject variability in digoxin bioavailability was noted whether the antidiarrheal was given 2 hr before or 2 hr after the cardiac glycoside.

Adult↗
PubMed1977

Effect of lidocaine on the absorption, disposition and tolerance of intramuscularly administered cefoxitin.

The use of lidocaine HCL solution at concentrations of 0.5 and 1.0% to reconstitute sodium cefoxitin relieves the pain associated with intramuscular injections of the antibiotic. Cefoxitin absorption by the intramuscular route is initially rapid and is virtually complete. Peak serum concentrations, corresponding to about one-half those of a comparable intravenous infusion, are achieved in 30 min. Continuing absorption tends to maintain higher serum concentrations for longer times. Renal clearance and serum half-life of cefoxitin do not appear to be affected by lidocaine at its effective anaesthetic concentrations.

Absorption↗
PubMed1975

In vitro and in vivo availability of commercial prednisone tablets.

A three-way crossover bioavailability study was performed using nine adult male volunteers with three different commercial prednisone tablets. Plasma samples were assayed for prednisolone, the active metabolite of prednisone, by a radioimmunoassay method. Statistical analysis showed significant differences in the rate of appearance of prednisolone in plasma but not in the amount converted to prednisolone. The results suggest that differences in in vivo rates of appearance of prednisolone in plasma correlate with in vitro rates of dissolution.

Adult↗