William R. Gillespie

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Our objective was to develop a beta regression (BR) model to describe the longitudinal progression of the 11 item Alzheimer’s disease (AD) assessment scale cognitive subscale (ADAS-cog) in AD patients in both natural history and randomized clinical trial settings, utilizing both individual patient and summary level literature data. Patient data from the(More)
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(More)
A new deconvolution algorithm (DCON) suitable for pharmacokinetic applications is presented. It requires that both the impulse and input responses, typically systemic drug levels, be well described by polyexponential equations. DCON has a wider range of applications than an earlier method (DECONV) from which it is derived. A FORTRAN program is provided,(More)
Purpose. To theoretically investigate the impact of gastric emptying half-time, intestinal transit time and the time for 85% in vivo dissolution on the peak concentration and area-under-the curve of model drugs. Methods. Simulations were performed using mathematical models of gastrointestinal physiology and pharmacokinetics of model drugs with different(More)
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(More)
metrumrg is an R package that facilitates workflow for the discipline of pharmacometrics. Support is provided for data preparation, modeling, simulation, diagnostics, and reporting. Existing tools and techniques are emphasized where available; original solutions are provided for otherwise unmet needs. In particular, metrumrg implements an R interface for(More)
The authors frequently mention the value of PBPK in regard to their "regulatory customers," apparently referring to the Food and Drug Administration and other regulatory agencies worldwide. It can be argued that too narrow of a focus on the regulatory customer will poorly serve the true customers, the patients who will receive the drug product. In turn,(More)
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(More)
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,(More)