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Biomedical subjects

W R Gillespie

Publications and source records attributed to W R Gillespie.

46 records · Page 3Linked to original sources
PubMed1982

Relative bioavailability of commercially available ibuprofen oral dosage forms in humans.

Two human bioavailability studies were conducted to assess the in vivo performances of recently marketed 200-, 300-, and 400-mg ibuprofen capsules relative to the innovator's 300- and 400-mg tablets when administered as single oral 300- or 400-mg doses. An ibuprofen oral solution was also administered in each trial. Within each study, the products were equivalent to each other and to the oral solution with respect to the extent of ibuprofen absorption. Absorption rates, however, differed markedly among the products studied. Ibuprofen was more slowly absorbed from the 300- and 400-mg capsules than from the respective strength tablets. The 200-mg capsule exhibited an absorption rate comparable to the 400-mg tablet but more rapid than the 400-mg capsule. It was concluded that two of the duplicator's 200-mg capsules were bioequivalent to one of the innovator's 400-mg tablet. The duplicator's 300- and 400-mg capsules were bioinequivalent to the innovator's 300- and 400-mg tablets, respectively, due to their slower rates of absorption.

Adolescent↗
PubMed1982

Bioavailability of tolazamide from tablets: comparison of in vitro and in vivo results.

The relative bioavailability of tolazamide was determined, in healthy male volunteers, from four different tablet formulations manufactured by direct compaction or granulation processes and the results were compared with in vitro disintegration and dissolution values. Serum tolazamide levels were determined by a high-pressure liquid chromatographic method developed in this laboratory. Serum tolazamide levels from the formulation that gave rise to rapid absorption were described by one-compartment model kinetics with a mean absorption half-time of 1.0 hr and an elimination half-life of 4.6 hr. Peak serum levels occurred at 3.3 hr after drug administration. Marked differences were observed in drug bioavailability from the four tablets, and the mean cumulative relative fraction of dose absorbed was 1.0, 0.42, 0.75, and 0.91 from Formulations A, B, C, and D, respectively. The hypoglycemic effect was closely related to serum tolazamide levels. Disintegration times did not predict in vivo tolazamide bioavailability. Dissolution rates provided an approximate rank order correlation with in vivo absorption but failed to be predictive among formulations. Currently available in vitro tests do not accurately predict tolazamide in vivo bioavailability characteristics among different formulations and manufacturing processes but may be useful to ensure lot-to-lot uniformity in bioavailability for a given formulation and specific method of manufacture.

Adolescent↗
PubMed1982

The effect of food on the bioavailability and pharmacodynamics of tolbutamide in diabetic patients.

The effect of food on the rate and extent of absorption of tolbutamide in diabetic patients was studied by varying the time of drug administration in relation to the ingestion of a standard meal. Serum levels of tolbutamide, insulin and glucose and related bioavailability parameters were compared following the administration of a single dose of tolbutamide 0.5 g to diabetic patients 30 min prior to and immediately before a standardized meal. A placebo dosage form was also administered to determine baseline glucose and insulin response to the meal. The 700 calorie standard meal was composed of 41% carbohydrate, 18% protein, and 41% fat. Administration of the drug with the meal resulted in a 6% (statistically significant) decrease in the extent of absorption, as determined by measurement of the area under the tolbutamide serum level-time curve from zero to infinity. Serum levels of tolbutamide were also significantly higher 0.5 h after drug administration when the drug was taken with the meal. Except for these two minor effects, no other differences between the drug treatments were observed in any other parameters of tolbutamide absorption or in the postprandial glucose and insulin serum levels. Therefore, the small differences found were judged to be clinically meaningless. These findings demonstrate that administration of tolbutamide 0.5 g tablets 30 min prior to or with a standard meal results in equivalent therapeutic actions.

Adult↗
PubMed1981

Reversible metabolism and pharmacokinetics: application to prednisone-prednisolone.

The simplest three pharmacokinetic models which apply in cases of reversible metabolism are described. Area under the curve (AUC) relationships are described which allow one to make a choice of which one of the three models may apply in a particular case. Expressions for clearances and other pharmacokinetic parameters are given. It is shown that biexponential time courses are expected after bolus intravenous administration although distribution is not involved in the models. In some cases dose/AUC or infusion rate/steady-state concentration yield simple clearances, while in other cases they are complex. AUC data obtained following oral administration of 5 mg doses of prednisone and prednisolone to 16 normal volunteers were analyzed with the new concepts and one of the models was found to apply. This new interpretation of such data results in some significant changes from application of classical pharmacokinetics.

Adolescent↗
PubMedDate not supplied

Effect of injection volume on the bioavailability of sterile medroxyprogesterone acetate suspension.

The influence of injection volume on the absorption and bioavailability of medroxyprogesterone acetate (MPA) was studied. A single i.m. injection of MPA 400 mg was administered to 24 healthy men; 12 of the subjects received 4 ml of a 100 mg/ml suspension of the drug, and the other 12 subjects were given 1 ml of a 400 mg/ml suspension. Blood samples for MPA determinations were collected periodically during a 202-day period after drug administration. Mean steady-state serum concentrations of MPA were simulated from single-dose data to reflect those achieved after standard dosage regimens. Values for area under the serum concentration-time curve and time required to reach peak serum concentrations were compared between subjects receiving different injection volumes of MPA. Mean peak serum concentration were significantly higher and occurred significantly sooner in subjects receiving the 4-ml injection of MPA than in those given the 1-ml injection. No significant differences in areas under the serum concentration-time curve were noted in subjects receiving different injection volumes. The rate but not the extent of absorption of injectable MPA suspension is enhanced by increasing the injection volume of equivalent doses from 1 ml to 4 ml.

Adult↗