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C C Peck

Publications and source records attributed to C C Peck.

At least 37 records · Page 2Linked to original sources
PubMed1994

The essential role of integrative biomedical sciences in protecting and contributing to the health and well-being of our nation.

The biomedical sciences in the United States are currently experiencing the effects of an increased emphasis on in vitro models of biological and disease processes. Advances in cellular and subcellular biology have been a driving force in the funding of new research, the training of new scientists, and new drug discovery and development. The importance of new findings at the cellular and subcellular levels is not disputed. However, the corresponding decline in funding and training opportunities for biologically relevant investigations at the level of the intact animal (including humans; hereafter designated as integrative biology) is a serious threat to continued biomedical advances. The lack of resources for integrative biology has far-reaching negative consequences in 1) the development and utilization of whole animal models of disease and dysfunction; 2) assessing the relevancy of in vitro studies to physiological mechanisms; 3) the evaluation of the scientific merit of whole animal investigations and their relevancy to the nation's scientific imperatives; 4) the instruction of young scientists in the technology and especially in the methods of integrative biology, including how to develop appropriate experimental hypotheses; 5) the instruction of graduate, medical, dental, pharmacy, and nursing students in drug and disease processes in the intact human; and 6) the ability of the pharmaceutical manufacturers, the FDA, the EPA and academia to hire scientists who can develop drugs and evaluate the effects of exogenous agents on the intact animal. These negative consequences can be alleviated in a variety of ways. These include 1) increasing the availability of funding for research in integrative biology, 2) increasing the opportunities for training in integrative biology, and 3) instituting grant reviews of integrative biomedical research by peers in integrative biomedical sciences. These measures can revitalize integrative biomedical research, help ensure the continued advancement of biomedical understanding, and consequently contribute to the alleviation of human suffering.

Animals↗
PubMed1992

Clinical pharmacology training at the Food & Drug Administration.

Challenged with the clearly demonstrated need for highly trained clinical pharmacologists for new drug development and review activities, the FDA Center for Drug Evaluation and Research (CDER) established an internal Staff College. This organizationally unique and innovative unit addressed the educational needs of both the new and the veteran CDER scientists. A multileveled strategy was conceptualized and implemented as described.

Curriculum↗
PubMed1992

Adaptive control with feedback strategies for suramin dosing.

Suramin, a drug used in the treatment of parasitic diseases, is currently being evaluated in clinical trials as an antineoplastic agent. The use of therapeutic drug monitoring and adaptive control with feedback in clinical trials of suramin was initially motivated by an association between acute neurologic toxicity and plasma suramin concentrations in excess of 350 micrograms/ml. We have prospectively examined the performance of both two- and three-compartment population pharmacokinetic models in controlling plasma suramin concentrations and have found that a three-compartment model best describes this drug. No correlation was found between the clearance of suramin and creatinine clearance, as had been previously hypothesized. The low systemic clearance of suramin and the number of parameters required to describe the three-compartment model suggest the need for a bayesian approach to the estimation of individual pharmacokinetics.

Adrenal Gland Neoplasms↗
PubMed1991

The randomized concentration-controlled trial: an evaluation of its sample size efficiency.

A randomized concentration-controlled trial (RCCT) is one in which subjects are randomly assigned to predetermined levels of average plasma drug concentration. These target concentrations can be achieved (within reasonable ranges) by an individualized pharmacokinetically controlled dosing scheme. The RCCT is designed to minimize the interindividual pharmacokinetic (PK) variability within comparison groups and consequently decrease the variability in clinical response within these groups. In this paper, we investigate the extent of improvement in sample size efficiency that can be gained from the RCCT design in comparison to the traditional randomized dose-controlled trial (RDCT) design. Our investigations involve both theoretical arguments and simulation studies, illustrated with data on PK and pharmacodynamic (PD) characteristics of the antiasthma drug theophylline. Aside from safety concerns that strongly suggest the use of RCCT for drugs with narrow therapeutic windows, sample size considerations favor the choice of RCCT in many situations, as shown in this paper.

Administration, Oral↗
PubMed1991

Transcutaneous chemical collection of caffeine in normal subjects: relationship to area under the plasma concentration-time curve and sweat production.

A novel transcutaneous chemical collection device (TCD) has been developed to study the phenomenon of outward transcutaneous chemical migration. The TCD is a Bandaid-like device containing an immobilized aqueous media and binding reservoir material to prevent back-transfer into the skin. This device, when placed against the skin, allows collection and quantitation of chemicals that diffuse directly through the skin from within the body. The relationship of the amount of drug collected in the TCD to the amount in the body available for collection (as represented by the area under the plasma-concentration time curve, AUC) and the effects of sweating, a potential confounding factor, on collection of drug in a TCD were studied, using caffeine as a model compound. TCD were placed on the skin of normal male volunteers. Twenty-four hours later subjects took caffeine by mouth. Blood samples were collected and TCD were removed at various times after drug intake and analyzed by HPLC for caffeine. Studies of the sweating effect were carried out in a similar manner, except that one arm of each subject was maintained at 40 degrees C to induce local sweating, the other arm acted as a non-sweating control. The amount of caffeine collected was linearly related to the AUC. Sweating seemed to have a large (40%) contribution to transdermal collection in the early period (5.5 h) of the study, but this difference was much less (14%) at longer collection times (10 h).

Adult↗
PubMed1990

Transcutaneous theophylline collection in preterm infants.

Transcutaneous collection of theophylline and its metabolite, caffeine, was undertaken in 33 preterm infants (2 to 89 days old) who were receiving routine theophylline therapy. Collection was done by means of a novel adhesive transcutaneous collection system. The transcutaneous collection system accumulated substances that migrated from the blood to the skin surface by trapping them in an activated charcoal-gel matrix. On one to three occasions, four transdermal collection systems were applied to the back or abdomen of each infant for 4 to 12 hours. During that time, blood samples were obtained for routine monitoring of plasma theophylline levels. Amounts of theophylline (95 +/- 198 ng) and caffeine (83 +/- 77 ng) in the transcutaneous collection system were significantly correlated with the respective average plasma drug concentration and postconceptional age (p less than 0.01). Skin reactions were limited to mild erythema. We concluded that theophylline and caffeine can be collected on the surface of the skin of preterm infants with a novel transcutaneous collection system. Amounts collected by means of the transcutaneous collection system correlated with plasma concentrations consistent with a diffusion process, but they were poor predictors of individual concentrations.

Age Factors↗
PubMed1990

An evaluation of Bayesian microcomputer predictions of theophylline concentrations in newborn infants.

Determination of appropriate theophylline maintenance doses in preterm infants is confounded by interpatient variability. This study evaluated the performance of an IBM PC computer program applying Bayesian regression before and during steady state in 37 preterm infants. Prior population estimates of clearance and distribution volume in preterm infants and Bayesian estimates of clearance and distribution volume based on one to three theophylline plasma concentrations were used to predict subsequent concentrations (drawn 1-17 days later). We assessed the accuracy and precision of the predictive performance of the Bayesian program with the mean prediction error and the mean absolute prediction error. The absolute prediction error (mean absolute error +/- SEM) significantly decreased with increasing feedback concentrations from 3.54 +/- 0.45 micrograms/ml (population estimates) to 2.74 +/- 0.42 (one feedback) and 2.02 +/- 0.35 micrograms/ml (two feedback concentrations). Mean prediction errors (+/- SEM) based on one to three feedbacks (-1.5 +/- 0.40 micrograms/ml) were significant improvements over population predictions (-2.63 +/- 0.72 micrograms/ml, p less than 0.05), although a small but significant average overprediction remained. Absolute prediction error was correlated with postconceptional and postnatal age when zero or one but not two feedback concentrations were available. Computer program predictions based on one measured feedback concentration were more accurate and precise than population-based predictions. Refinement of population parameters or two feedback concentrations further improved performance.

Bayes Theorem↗
PubMed1990

Noninvasive transdermal chemical collection. I. In vitro adsorption characteristics of gel/charcoal matrices.

We characterized in vitro adsorption of representative chemicals in candidate gel/charcoal matrices being investigated for use in noninvasive transdermal chemical collection. Binding properties of three model compounds of widely varying water and lipid solubilities (theophylline, methotrexate, and parathion) were studied in hydrophilic (agarose, or polyvinyl alcohol/polyvinyl pyrrolidone) and lipophilic (silicone) gel/charcoal compositions. Analysis of adsorption isotherms indicate that agarose is the superior gel selection for hydrophilic compounds such as theophylline and methotrexate (greater than 90% uptake for each), and that a silicone lipogel allows for greatest lipophilic (parathion) adsorption (greater than 95% uptake).

Absorption↗
PubMed1990

Noninvasive transdermal chemical collection. II. In vitro and in vivo skin permeability studies.

In vitro and in vivo skin permeability studies were conducted to investigate properties of several candidate transdermal chemical collection devices (TCDs). The TCD consists of a binding reservoir of activated charcoal suspended in a gel medium which is occlusively placed in direct contact with the skin. Binding of three model compounds (theophylline, methotrexate, and parathion) was studied in hydrophilic (agarose or PVA/PVP) and lipophilic (silicone) gel/carbon compositions. The effects of gel composition, compound hydrophilicity/lipophilicity, and hydration of skin on quantity of transdermally collected chemical and 'apparent' permeability were investigated using a 'fuzzy' rat animal model. In vitro and in vivo apparent permeability coefficients (Kp; cm/h) for amphophilic theophylline (6.95 x 10(-4) and 8.34 x 10(-4), respectively) and hydrophilic methotrexate (3.5 x 10(-3) and 3.2 x 10(-4), respectively) using an agarose aquagel TCD were greater than the corresponding Kp values obtained when silicone lipogel TCDs were employed (0.3 x 10(-4) and 3.2 x 10(-4), respectively, for theophylline; no measurable methotrexate was collected). Occlusive hydration of skin profoundly increased permeability of the hydrophyilic model compound, methotrexate. In vivo Kp values for lipophilic parathion were greater with a silicone TCD (6.7 x 10(-4) than with an agarose TCD (3.8 x 10(-4). We conclude that it is possible to influence transdermal chemical collection through modifications in the gel composition and by hydration of the skin.

Animals↗